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  • 1. Abbas, S
    et al.
    Linseisen, J
    Rohrmann, S
    Beulens, JWJ
    Buijsse, B
    Amiano, P
    Ardanaz, E
    Balkau, B
    Boeing, H
    Clavel-Chapelon, F
    Fagherazzi, G
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Gavrila, D
    Grioni, S
    Kaaks, R
    Key, TJ
    Khaw, KT
    Kuehn, T
    Mattiello, A
    Molina-Montes, E
    Nilsson, PM
    Overvad, K
    Quiros, JR
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Sacerdote, C
    Saieva, C
    Slimani, N
    Sluijs, I
    Spijkerman, AMW
    Tjonneland, A
    Tumino, R
    van der A, DL
    Zamora-Ros, R
    Sharp, SJ
    Langenberg, C
    Forouhi, NG
    Riboli, E
    Wareham, NJ
    Dietary vitamin D intake and risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition: the EPIC-InterAct study2014Ingår i: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 68, nr 2, s. 196-202Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND/OBJECTIVES: Prospective cohort studies have indicated that serum vitamin D levels are inversely related to risk of type 2 diabetes. However, such studies cannot determine the source of vitamin D. Therefore, we examined the association of dietary vitamin D intake with incident type 2 diabetes within the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study in a heterogeneous European population including eight countries with large geographical variation.

    SUBJECTS/METHODS: Using a case-cohort design, 11 245 incident cases of type 2 diabetes and a representative subcohort (N = 15 798) were included in the analyses. Hazard ratios (HR) and 95% confidence intervals (CIs) for type 2 diabetes were calculated using a Prentice-weighted Cox regression adjusted for potential confounders. Twenty-four-hour diet-recall data from a subsample (N = 2347) were used to calibrate habitual intake data derived from dietary questionnaires.

    RESULTS: Median follow-up time was 10.8 years. Dietary vitamin D intake was not significantly associated with the risk of type 2 diabetes. HR and 95% CIs for the highest compared to the lowest quintile of uncalibrated vitamin D intake was 1.09 (0.97-1.22) (P-trend = 0.17). No associations were observed in a sex-specific analysis. The overall pooled effect (HR (95% CI)) using the continuous calibrated variable was 1.00 (0.97-1.03) per increase of 1 mg/day dietary vitamin D.

    CONCLUSIONS: This observational study does not support an association between higher dietary vitamin D intake and type 2 diabetes incidence. This result has to be interpreted in light of the limited contribution of dietary vitamin D on the overall vitamin D status of a person.

  • 2. Ahmad, S
    et al.
    Poveda, A
    Shungin, Dmitry
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Umeå universitet, Medicinska fakulteten, Institutionen för odontologi. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Center, Lund University, Malmö, Sweden.
    Barroso, I
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Renström, Frida
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Center, Lund University, Malmö, Sweden.
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Center, Lund University, Malmö, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
    Established BMI-associated genetic variants and their prospective associations with BMI and other cardiometabolic traits: the GLACIER Study2016Ingår i: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 40, nr 9, s. 1346-1352Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Recent cross-sectional genome-wide scans have reported associations of 97 independent loci with body mass index (BMI). In 3541 middle-aged adult participants from the GLACIER Study, we tested whether these loci are associated with 10-year changes in BMI and other cardiometabolic traits (fasting and 2-h glucose, triglycerides, total cholesterol, and systolic and diastolic blood pressures).

    METHODS: A BMI-specific genetic risk score (GRS) was calculated by summing the BMI-associated effect alleles at each locus. Trait-specific cardiometabolic GRSs comprised only the loci that show nominal association (P⩽0.10) with the respective trait in the original cross-sectional study. In longitudinal genetic association analyses, the second visit trait measure (assessed ~10 years after baseline) was used as the dependent variable and the models were adjusted for the baseline measure of the outcome trait, age, age(2), fasting time (for glucose and lipid traits), sex, follow-up time and population substructure.

    RESULTS: The BMI-specific GRS was associated with increased BMI at follow-up (β=0.014 kg m(-2) per allele per 10-year follow-up, s.e.=0.006, P=0.019) as were three loci (PARK2 rs13191362, P=0.005; C6orf106 rs205262, P=0.043; and C9orf93 rs4740619, P=0.01). Although not withstanding Bonferroni correction, a handful of single-nucleotide polymorphisms was nominally associated with changes in blood pressure, glucose and lipid levels.

    CONCLUSIONS: Collectively, established BMI-associated loci convey modest but statistically significant time-dependent associations with long-term changes in BMI, suggesting a role for effect modification by factors that change with time in this population.

  • 3. Ahmad, Shafqat
    et al.
    Mora, Samia
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA; Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Clinical Research Centre, Lund University, Skåne University Hospital, Malmö, Sweden.
    Orho-Melander, Marju
    Ridker, Paul M.
    Hu, Frank B.
    Chasman, Daniel I.
    Adiposity and Genetic Factors in Relation to Triglycerides and Triglyceride-Rich Lipoproteins in the Women's Genome Health Study2018Ingår i: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 64, nr 1, s. 231-241Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Previous results from Scandinavian cohorts have shown that obesity accentuates the effects of common genetic susceptibility variants on increased triglycerides (TG). Whether such interactions are present in the US population and further selective for particular TG-rich lipoprotein subfractions is unknown.

    METHODS: We examined these questions using body mass index (BMI) and waist circumference (WC) among women of European ancestry from the Women's Genome Health Study (WGHS) (n = 21840 for BMI; n = 19313 for WC). A weighted genetic risk score (TG-wGRS) based on 40 published TG-associated single-nucleotide polymorphisms was calculated using published effect estimates.

    RESULTS: Comparing overweight (BMI ≥ 25 kg/m2) and normal weight (BMI < 25 kg/m2) WGHS women, each unit increase of TG-wGRS was associated with TG increases of 1.013% and 1.011%, respectively, and this differential association was significant (Pinteraction = 0.014). Metaanalyses combining results for WGHS BMI with the 4 Scandinavian cohorts (INTER99, HEALTH2006, GLACIER, MDC) (total n = 40026) yielded a more significant interaction (Pinteraction = 0.001). Similarly, we observed differential association of the TG-wGRS with TG (Pinteraction = 0.006) in strata of WC (<80 cm vs ≥80 cm). Metaanalysis with 2 additional cohorts reporting WC (INTER99 and HEALTH2006) (total n = 27834) was significant with consistent effects (Pinteraction = 0.006). We also observed highly significant interactions of the TG-wGRS across the strata of BMI with very large, medium, and small TG-rich lipoprotein subfractions measured by nuclear magnetic resonance spectroscopy (all Pinteractions < 0.0001). The differential effects were strongest for very large TG-rich lipoprotein.

    CONCLUSIONS: Our results support the original findings and suggest that obese individuals may be more susceptible to aggregated genetic risk associated with common TG-raising alleles, with effects accentuated in the large TG-rich lipoprotein subfraction.

  • 4. Ahmad, Shafqat
    et al.
    Rukh, Gull
    Varga, Tibor V
    Ali, Ashfaq
    Kurbasic, Azra
    Shungin, Dmitry
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Umeå universitet, Medicinska fakulteten, Institutionen för odontologi. Lund University.
    Ericson, Ulrika
    Koivula, Robert W
    Chu, Audrey Y
    Rose, Lynda M
    Ganna, Andrea
    Qi, Qibin
    Stancakova, Alena
    Sandholt, Camilla H
    Elks, Cathy E
    Curhan, Gary
    Jensen, Majken K
    Tamimi, Rulla M
    Allin, Kristine H
    Jorgensen, Torben
    Brage, Soren
    Langenberg, Claudia
    Aadahl, Mette
    Grarup, Niels
    Linneberg, Allan
    Pare, Guillaume
    Magnusson, Patrik KE
    Pedersen, Nancy L
    Boehnke, Michael
    Hamsten, Anders
    Mohlke, Karen L
    Pasquale, Louis T
    Pedersen, Oluf
    Scott, Robert A
    Ridker, Paul M
    Ingelsson, Erik
    Laakso, Markku
    Hansen, Torben
    Qi, Lu
    Wareham, Nicholas J
    Chasman, Daniel I
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Hu, Frank B
    Renström, Frida
    Orho-Melander, Marju
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Lund University and Harvard University.
    Gene x physical activity interactions in obesity: combined analysis of 111,421 individuals of European ancestry2013Ingår i: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 9, nr 7, s. e1003607-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Numerous obesity loci have been identified using genome-wide association studies. A UK study indicated that physical activity may attenuate the cumulative effect of 12 of these loci, but replication studies are lacking. Therefore, we tested whether the aggregate effect of these loci is diminished in adults of European ancestry reporting high levels of physical activity. Twelve obesity-susceptibility loci were genotyped or imputed in 111,421 participants. A genetic risk score (GRS) was calculated by summing the BMI-associated alleles of each genetic variant. Physical activity was assessed using self-administered questionnaires. Multiplicative interactions between the GRS and physical activity on BMI were tested in linear and logistic regression models in each cohort, with adjustment for age, age(2), sex, study center (for multicenter studies), and the marginal terms for physical activity and the GRS. These results were combined using meta-analysis weighted by cohort sample size. The meta-analysis yielded a statistically significant GRS x physical activity interaction effect estimate (P-interaction = 0.015). However, a statistically significant interaction effect was only apparent in North American cohorts (n = 39,810, P-interaction = 0.014 vs. n = 71,611, P-interaction = 0.275 for Europeans). In secondary analyses, both the FTO rs1121980 (P-interaction = 0.003) and the SEC16B rs10913469 (P-interaction = 0.025) variants showed evidence of SNP x physical activity interactions. This meta-analysis of 111,421 individuals provides further support for an interaction between physical activity and a GRS in obesity disposition, although these findings hinge on the inclusion of cohorts from North America, indicating that these results are either population-specific or non-causal.

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  • 5. Ahmad, Shafqat
    et al.
    Varga, Tibor V
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Gene x environment interactions in obesity: the state of the evidence2013Ingår i: Human Heredity, ISSN 0001-5652, E-ISSN 1423-0062, Vol. 75, nr 2-4, s. 106-115Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background/Aims: Obesity is a pervasive and highly prevalent disease that poses substantial health risks to those it affects. The rapid emergence of obesity as a global epidemic and the patterns and distributions of the condition within and between populations suggest that interactions between inherited biological factors (e.g. genes) and relevant environmental factors (e.g. diet and physical activity) may underlie the current obesity epidemic.

    Methods: We discuss the rationale for the assertion that gene x lifestyle interactions cause obesity, systematically appraise relevant literature, and consider knowledge gaps future studies might seek to bridge. Results: We identified >200 relevant studies, of which most are relatively small scale and few provide replication data.

    Conclusion: Although studies on gene x lifestyle interactions in obesity point toward the presence of such interactions, improved data standardization, appropriate pooling of data and resources, innovative study designs, and the application of powerful statistical methods will be required if translatable examples of gene x lifestyle interactions in obesity are to be identified. Future studies, of which most will be observational, should ideally be accompanied by appropriate replication data and, where possible, by analogous findings from experimental settings where clinically relevant traits (e.g. weight regain and weight cycling) are outcomes.

    (C) 2013 S. Karger AG, Basel

  • 6.
    Ahmad, Shafqat
    et al.
    Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Zhao, Wei
    Philadelphia, PA, US.
    Renström, Frida
    Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Rasheed, Asif
    Karachi, Pakistan.
    Samuel, Maria
    Karachi, Pakistan.
    Zaidi, Mozzam
    Karachi, Pakistan.
    Shah, Nabi
    Karachi, Pakistan; Abbottabad, Pakistan.
    Mallick, Nadeem Hayyat
    Punjab Institute of Cardiology, Lahore, Pakistan.
    Zaman, Khan Shah
    Karachi, Pakistan.
    Ishaq, Mohammad
    Karachi, Pakistan.
    Rasheed, Syed Zahed
    Karachi, Pakistan.
    Memon, Fazal-ur-Rheman
    Karachi, Pakistan.
    Hanif, Bashir
    Karachi, Pakistan.
    Lakhani, Muhammad Shakir
    Karachi, Pakistan.
    Ahmed, Faisal
    Karachi, Pakistan.
    Kazmi, Shahana Urooj
    Karachi, Pakistan.
    Frossard, Philippe
    Karachi, Pakistan; Nazarbayev University, Astana, Kazakhstan.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Malmö, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
    Saleheen, Danish
    Philadelphia, PA, US; Karachi, Pakistan.
    Physical activity, smoking, and genetic predisposition to obesity in people from Pakistan: the PROMIS study2015Ingår i: BMC Medical Genetics, E-ISSN 1471-2350, Vol. 16, artikel-id 114Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Multiple genetic variants have been reliably associated with obesity-related traits in Europeans, but little is known about their associations and interactions with lifestyle factors in South Asians.

    Methods: In 16,157 Pakistani adults (8232 controls; 7925 diagnosed with myocardial infarction [MI]) enrolled in the PROMIS Study, we tested whether: a) BMI-associated loci, individually or in aggregate (as a genetic risk score - GRS), are associated with BMI; b) physical activity and smoking modify the association of these loci with BMI. Analyses were adjusted for age, age(2), sex, MI (yes/no), and population substructure.

    Results: Of 95 SNPs studied here, 73 showed directionally consistent effects on BMI as reported in Europeans. Each additional BMI-raising allele of the GRS was associated with 0.04 (SE = 0.01) kg/m(2) higher BMI (P = 4.5 x 10(-14)). We observed nominal evidence of interactions of CLIP1 rs11583200 (P-interaction = 0.014), CADM2 rs13078960 (P-interaction = 0.037) and GALNT10 rs7715256 (P-interaction = 0.048) with physical activity, and PTBP2 rs11165643 (P-interaction = 0.045), HIP1 rs1167827 (P-interaction = 0.015), C6orf106 rs205262 (P-interaction = 0.032) and GRID1 rs7899106 (P-interaction = 0.043) with smoking on BMI.

    Conclusions: Most BMI-associated loci have directionally consistent effects on BMI in Pakistanis and Europeans. There were suggestive interactions of established BMI-related SNPs with smoking or physical activity.

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  • 7. Albrechtsen, A.
    et al.
    Grarup, N.
    Li, Y.
    Sparso, T.
    Tian, G.
    Cao, H.
    Jiang, T.
    Kim, S. Y.
    Korneliussen, T.
    Li, Q.
    Nie, C.
    Wu, R.
    Skotte, L.
    Morris, A. P.
    Ladenvall, C.
    Cauchi, S.
    Stancakova, A.
    Andersen, G.
    Astrup, A.
    Banasik, K.
    Bennett, A. J.
    Bolund, L.
    Charpentier, G.
    Chen, Y.
    Dekker, J. M.
    Doney, A. S. F.
    Dorkhan, M.
    Forsen, T.
    Frayling, T. M.
    Groves, C. J.
    Gui, Y.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Hattersley, A. T.
    He, K.
    Hitman, G. A.
    Holmkvist, J.
    Huang, S.
    Jiang, H.
    Jin, X.
    Justesen, J. M.
    Kristiansen, K.
    Kuusisto, J.
    Lajer, M.
    Lantieri, O.
    Li, W.
    Liang, H.
    Liao, Q.
    Liu, X.
    Ma, T.
    Ma, X.
    Manijak, M. P.
    Marre, M.
    Mokrosinski, J.
    Morris, A. D.
    Mu, B.
    Nielsen, A. A.
    Nijpels, G.
    Nilsson, P.
    Palmer, C. N. A.
    Rayner, N. W.
    Renstrom, F.
    Ribel-Madsen, R.
    Robertson, N.
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Rossing, P.
    Schwartz, T. W.
    Slagboom, P. E.
    Sterner, M.
    Tang, M.
    Tarnow, L.
    Tuomi, T.
    van't Riet, E.
    van Leeuwen, N.
    Varga, T. V.
    Vestmar, M. A.
    Walker, M.
    Wang, B.
    Wang, Y.
    Wu, H.
    Xi, F.
    Yengo, L.
    Yu, C.
    Zhang, X.
    Zhang, J.
    Zhang, Q.
    Zhang, W.
    Zheng, H.
    Zhou, Y.
    Altshuler, D.
    't Hart, L. M.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Balkau, B.
    Froguel, P.
    McCarthy, M. I.
    Laakso, M.
    Groop, L.
    Christensen, C.
    Brandslund, I.
    Lauritzen, T.
    Witte, D. R.
    Linneberg, A.
    Jorgensen, T.
    Hansen, T.
    Wang, J.
    Nielsen, R.
    Pedersen, O.
    Exome sequencing-driven discovery of coding polymorphisms associated with common metabolic phenotypes2013Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 56, nr 2, s. 298-310Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Human complex metabolic traits are in part regulated by genetic determinants. Here we applied exome sequencing to identify novel associations of coding polymorphisms at minor allele frequencies (MAFs) > 1% with common metabolic phenotypes. The study comprised three stages. We performed medium-depth (8x) whole exome sequencing in 1,000 cases with type 2 diabetes, BMI > 27.5 kg/m(2) and hypertension and in 1,000 controls (stage 1). We selected 16,192 polymorphisms nominally associated (p < 0.05) with case-control status, from four selected annotation categories or from loci reported to associate with metabolic traits. These variants were genotyped in 15,989 Danes to search for association with 12 metabolic phenotypes (stage 2). In stage 3, polymorphisms showing potential associations were genotyped in a further 63,896 Europeans. Exome sequencing identified 70,182 polymorphisms with MAF > 1%. In stage 2 we identified 51 potential associations with one or more of eight metabolic phenotypes covered by 45 unique polymorphisms. In meta-analyses of stage 2 and stage 3 results, we demonstrated robust associations for coding polymorphisms in CD300LG (fasting HDL-cholesterol: MAF 3.5%, p = 8.5 x 10(-14)), COBLL1 (type 2 diabetes: MAF 12.5%, OR 0.88, p = 1.2 x 10(-11)) and MACF1 (type 2 diabetes: MAF 23.4%, OR 1.10, p = 8.2 x 10(-10)). We applied exome sequencing as a basis for finding genetic determinants of metabolic traits and show the existence of low-frequency and common coding polymorphisms with impact on common metabolic traits. Based on our study, coding polymorphisms with MAF above 1% do not seem to have particularly high effect sizes on the measured metabolic traits.

  • 8. Ali, Ashfaq
    et al.
    Varga, Tibor V.
    Stojkovic, Ivana A.
    Schulz, Christina-Alexandra
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Barroso, Ines
    Poveda, Alaitz
    Renström, Frida
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Orho-Melander, Marju
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.
    Do Genetic Factors Modify the Relationship Between Obesity and Hypertriglyceridemia?: Findings From the GLACIER and the MDC Studies2016Ingår i: Circulation: Cardiovascular Genetics, ISSN 1942-325X, E-ISSN 1942-3268, Vol. 9, nr 2, s. 162-171Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Obesity is a major risk factor for dyslipidemia, but this relationship is highly variable. Recently published data from 2 Danish cohorts suggest that genetic factors may underlie some of this variability.

    Methods and Results We tested whether established triglyceride-associated loci modify the relationship of body mass index (BMI) and triglyceride concentrations in 2 Swedish cohorts (the Gene-Lifestyle Interactions and Complex Traits Involved in Elevated Disease Risk [GLACIER Study; N=4312] and the Malmo Diet and Cancer Study [N=5352]). The genetic loci were amalgamated into a weighted genetic risk score (WGRS(TG)) by summing the triglyceride-elevating alleles (weighted by their established marginal effects) for all loci. Both BMI and the WGRS(TG) were strongly associated with triglyceride concentrations in GLACIER, with each additional BMI unit (kg/m(2)) associated with 2.8% (P=8.4x10(-84)) higher triglyceride concentration and each additional WGRS(TG) unit with 2% (P=7.6x10(-48)) higher triglyceride concentration. Each unit of the WGRS(TG) was associated with 1.5% higher triglyceride concentrations in normal weight and 2.4% higher concentrations in overweight/obese participants (P-interaction=0.056). Meta-analyses of results from the Swedish cohorts yielded a statistically significant WGRS(TG)xBMI interaction effect (P-interaction=6.0x10(-4)), which was strengthened by including data from the Danish cohorts (P-interaction=6.5x10(-7)). In the meta-analysis of the Swedish cohorts, nominal evidence of a 3-way interaction (WGRS(TG)xBMIxsex) was observed (P-interaction=0.03), where the WGRS(TG)xBMI interaction was only statistically significant in females. Using protein-protein interaction network analyses, we identified molecular interactions and pathways elucidating the metabolic relationships between BMI and triglyceride-associated loci.

    Conclusions Our findings provide evidence that body fatness accentuates the effects of genetic susceptibility variants in hypertriglyceridemia, effects that are most evident in females.

  • 9. Allin, Kristine H.
    et al.
    Tremaroli, Valentina
    Caesar, Robert
    Jensen, Benjamin A. H.
    Damgaard, Mads T. F.
    Bahl, Martin I.
    Licht, Tine R.
    Hansen, Tue H.
    Nielsen, Trine
    Dantoft, Thomas M.
    Linneberg, Allan
    Jørgensen, Torben
    Vestergaard, Henrik
    Kristiansen, Karsten
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Hansen, Torben
    Bäckhed, Fredrik
    Pedersen, Oluf
    Aberrant intestinal microbiota in individuals with prediabetes2018Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, nr 4, s. 810-820Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims/hypothesis: Individuals with type 2 diabetes have aberrant intestinal microbiota. However, recent studies suggest that metformin alters the composition and functional potential of gut microbiota, thereby interfering with the diabetes-related microbial signatures. We tested whether specific gut microbiota profiles are associated with prediabetes (defined as fasting plasma glucose of 6.1-7.0 mmol/l or HbA1c of 42-48 mmol/mol [6.0-6.5%]) and a range of clinical biomarkers of poor metabolic health.

    Methods: In the present case-control study, we analysed the gut microbiota of 134 Danish adults with prediabetes, overweight, insulin resistance, dyslipidaemia and low-grade inflammation and 134 age-and sex-matched individuals with normal glucose regulation.

    Results: We found that five bacterial genera and 36 operational taxonomic units (OTUs) were differentially abundant between individuals with prediabetes and those with normal glucose regulation. At the genus level, the abundance of Clostridium was decreased (mean log2 fold change -0.64 (SEM 0.23), p adj = 0.0497), whereas the abundances of Dorea, [Ruminococcus], Sutterella and Streptococcus were increased (mean log2 fold change 0.51 (SEM 0.12), p adj = 5 x 10-4; 0.51 (SEM 0.11), p adj = 1 x 10-4; 0.60 (SEM 0.21), p adj = 0.0497; and 0.92 (SEM0.21), p adj = 4 x 10-4, respectively). The two OTUs that differed the most were a member of the order Clostridiales (OTU 146564) and Akkermansia muciniphila, which both displayed lower abundance among individuals with prediabetes (mean log2 fold change -1.74 (SEM0.41), p adj = 2 x 10-3 and -1.65 (SEM0.34), p adj = 4 x 10-4, respectively). Faecal transfer from donors with prediabetes or screen-detected, drug-naive type 2 diabetes to germfree Swiss Webster or conventional C57BL/6 J mice did not induce impaired glucose regulation in recipient mice.

    Conclusions/interpretation: Collectively, our data show that individuals with prediabetes have aberrant intestinal microbiota characterised by a decreased abundance of the genus Clostridium and the mucin-degrading bacterium A. muciniphila. Our findings are comparable to observations in overt chronic diseases characterised by low-grade inflammation.

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  • 10. Almqvist, Catarina
    et al.
    Adami, Hans-Olov
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Groop, Leif
    Ingelsson, Erik
    Kere, Juha
    Lissner, Lauren
    Litton, Jan-Eric
    Maeurer, Markus
    Michaëlsson, Karl
    Palmgren, Juni
    Pershagen, Göran
    Ploner, Alexander
    Sullivan, Patrick F
    Tybring, Gunnel
    Pedersen, Nancy L
    LifeGene: a large prospective population-based study of global relevance2011Ingår i: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 26, nr 1, s. 67-77Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Studying gene-environment interactions requires that the amount and quality of the lifestyle data is comparable to what is available for the corresponding genomic data. Sweden has several crucial prerequisites for comprehensive longitudinal biomedical research, such as the personal identity number, the universally available national health care system, continuously updated population and health registries and a scientifically motivated population. LifeGene builds on these strengths to bridge the gap between basic research and clinical applications with particular attention to populations, through a unique design in a research-friendly setting. LifeGene is designed both as a prospective cohort study and an infrastructure with repeated contacts of study participants approximately every 5 years. Index persons aged 18-45 years old will be recruited and invited to include their household members (partner and any children). A comprehensive questionnaire addressing cutting-edge research questions will be administered through the web with short follow-ups annually. Biosamples and physical measurements will also be collected at baseline, and re-administered every 5 years thereafter. Event-based sampling will be a key feature of LifeGene. The household-based design will give the opportunity to involve young couples prior to and during pregnancy, allowing for the first study of children born into cohort with complete pre-and perinatal data from both the mother and father. Questions and sampling schemes will be tailored to the participants' age and life events. The target of LifeGene is to enroll 500,000 Swedes and follow them longitudinally for at least 20 years.

  • 11. Ashar, Foram N.
    et al.
    Mitchell, Rebecca N.
    Albert, Christine M.
    Newton-Cheh, Christopher
    Brody, Jennifer A.
    Mueller-Nurasyid, Martina
    Moes, Anna
    Meitinger, Thomas
    Mak, Angel
    Huikuri, Heikki
    Junttila, M. Juhani
    Goyette, Philippe
    Pulit, Sara L.
    Pazoki, Raha
    Tanck, MichaelW.
    Blom, Marieke T.
    Zhao, XiaoQing
    Havulinna, Aki S.
    Jabbari, Reza
    Glinge, Charlotte
    Tragante, Vinicius
    Escher, Stefan A.
    Chakravarti, Aravinda
    Ehret, Georg
    Coresh, Josef
    Li, Man
    Prineas, Ronald J.
    Franco, Oscar H.
    Kwok, Pui-Yan
    Lumley, Thomas
    Dumas, Florence
    McKnight, Barbara
    Rotter, Jerome I.
    Lemaitre, Rozenn N.
    Heckbert, Susan R.
    O'Donnell, Christopher J.
    Hwang, Shih-Jen
    Tardif, Jean-Claude
    VanDenburgh, Martin
    Uitterlinden, Andre G.
    Hofman, Albert
    Stricker, Bruno H. C.
    de Bakker, Paul I. W.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Jansson, Jan-Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Asselbergs, Folkert W.
    Halushka, Marc K.
    Maleszewski, Joseph J.
    Tfelt-Hansen, Jacob
    Engstrom, Thomas
    Salomaa, Veikko
    Virmani, Renu
    Kolodgie, Frank
    Wilde, Arthur A. M.
    Tan, Hanno L.
    Bezzina, Connie R.
    Eijgelsheim, Mark
    Rioux, John D.
    Jouven, Xavier
    Kääb, Stefan
    Psaty, Bruce M.
    Siscovick, David S.
    Arking, Dan E.
    Sotoodehnia, Nona
    A comprehensive evaluation of the genetic architecture of sudden cardiac arrest2018Ingår i: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 39, nr 44, s. 3961-+Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims: Sudden cardiac arrest (SCA) accounts for 10% of adult mortality in Western populations. We aim to identify potential loci associated with SCA and to identify risk factors causally associated with SCA.

    Methods and results: We carried out a large genome-wide association study (GWAS) for SCA (n = 3939 cases, 25 989 non-cases) to examine common variation genome-wide and in candidate arrhythmia genes. We also exploited Mendelian randomization (MR) methods using cross-trait multi-variant genetic risk score associations (GRSA) to assess causal relationships of 18 risk factors with SCA. No variants were associated with SCA at genome-wide significance, nor were common variants in candidate arrhythmia genes associated with SCA at nominal significance. Using cross-trait GRSA, we established genetic correlation between SCA and (i) coronary artery disease (CAD) and traditional CAD risk factors (blood pressure, lipids, and diabetes), (ii) height and BMI, and (iii) electrical instability traits (QT and atrial fibrillation), suggesting aetiologic roles for these traits in SCA risk.

    Conclusions: Our findings show that a comprehensive approach to the genetic architecture of SCA can shed light on the determinants of a complex life-threatening condition with multiple influencing factors in the general population. The results of this genetic analysis, both positive and negative findings, have implications for evaluating the genetic architecture of patients with a family history of SCA, and for efforts to prevent SCA in high-risk populations and the general community.

  • 12. Atabaki-Pasdar, Naeimeh
    et al.
    Ohlsson, Mattias
    Shungin, Dmitry
    Kurbasic, Azra
    Ingelsson, Erik
    Pearson, Ewan R.
    Ali, Ashfaq
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, SE-205 02, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
    Statistical power considerations in genotype-based recall randomized controlled trials2016Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 6, artikel-id 37307Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Randomized controlled trials (RCT) are often underpowered for validating gene-treatment interactions. Using published data from the Diabetes Prevention Program (DPP), we examined power in conventional and genotype-based recall (GBR) trials. We calculated sample size and statistical power for genemetformin interactions (vs. placebo) using incidence rates, gene-drug interaction effect estimates and allele frequencies reported in the DPP for the rs8065082 SLC47A1 variant, a metformin transported encoding locus. We then calculated statistical power for interactions between genetic risk scores (GRS), metformin treatment and intensive lifestyle intervention (ILI) given a range of sampling frames, clinical trial sample sizes, interaction effect estimates, and allele frequencies; outcomes were type 2 diabetes incidence (time-to-event) and change in small LDL particles (continuous outcome). Thereafter, we compared two recruitment frameworks: GBR (participants recruited from the extremes of a GRS distribution) and conventional sampling (participants recruited without explicit emphasis on genetic characteristics). We further examined the influence of outcome measurement error on statistical power. Under most simulated scenarios, GBR trials have substantially higher power to observe gene-drug and gene-lifestyle interactions than same-sized conventional RCTs. GBR trials are becoming popular for validation of gene-treatment interactions; our analyses illustrate the strengths and weaknesses of this design.

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  • 13. Barroso, I
    et al.
    Luan, J
    Sandhu, MS
    Franks, Paul
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin.
    Crowley, V
    Meta-analysis of the Gly482Ser variant in PPARGC1A in type 2 diabetes and related phenotypes.2006Ingår i: Diabetologia, Vol. 49, nr 3, s. 501-5Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIMS/HYPOTHESIS: Peroxisome proliferator-activated receptor-gamma co-activator-1alpha (PPARGC1A) is a transcriptional co-activator with a central role in energy expenditure and glucose metabolism. Several studies have suggested that the common PPARGC1A polymorphism Gly482Ser may be associated with risk of type 2 diabetes, with conflicting results. To clarify the role of Gly482Ser in type 2 diabetes and related human metabolic phenotypes we genotyped this polymorphism in a case-control study and performed a meta-analysis of relevant published data. MATERIALS AND METHODS: Gly482Ser was genotyped in a type 2 diabetes case-control study (N=1,096) using MassArray technology. A literature search revealed publications that examined Gly482Ser for association with type 2 diabetes and related metabolic phenotypes. Meta-analysis of the current study and relevant published data was undertaken. RESULTS: In the pooled meta-analysis, including data from this study and seven published reports (3,718 cases, 4,818 controls), there was evidence of between-study heterogeneity (p<0.1). In the fixed-effects meta-analysis, the pooled odds ratio for risk of type 2 diabetes per Ser482 allele was 1.07 (95% CI 1.00-1.15, p=0.044). Elimination of one of the studies from the meta-analysis gave a summary odds ratio of 1.11 (95% CI 1.04-1.20, p=0.004), with no between-study heterogeneity (p=0.475). For quantitative metabolic traits in normoglycaemic subjects, we also found significant between-study heterogeneity. However, no significant association was observed between Gly482Ser and BMI, fasting glucose or fasting insulin. CONCLUSIONS/INTERPRETATION: This meta-analysis of data from the current and published studies supports a modest role for the Gly482Ser PPARGC1A variant in type 2 diabetes risk.

  • 14. Bennet, L.
    et al.
    Groop, L.
    Lindblad, U.
    Agardh, C-D
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Clinical Sciences, Lund University, Malmö, Sweden and Genetic & Molecular Epidemiology Unit, Lund University, Malmö, Sweden and Department of Nutrition, Harvard School of Public Health, Boston Massachusetts, USA.
    Ethnicity is an independent risk indicator when estimating diabetes risk with FINDRISC scores: A cross sectional study comparing immigrants from the Middle East and native Swedes2014Ingår i: Primary Care Diabetes, ISSN 1751-9918, E-ISSN 1878-0210, Vol. 8, nr 3, s. 231-238Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims: This study sought to compare type 2 diabetes (T2D) risk indicators in Iraqi immigrants with those in ethnic Swedes living in southern Sweden. Methods: Population-based, cross-sectional cohort study of men and women, aged 30-75 years, born in Iraq or Sweden conducted in 2010-2012 in Malmo, Sweden. A 75 g oral glucose tolerance test was performed and sociodemographic and lifestyle data were collected. T2D risk was assessed by the Finnish Diabetes Risk Score (FINDRISC). Results: In Iraqi versus Swedish participants, T2D was twice as prevalent (11.6 vs. 5.8%, p < 0.001). A large proportion of the excess T2D risk was attributable to larger waist circumference and first-degree family history of diabetes. However, Iraqi ethnicity was a risk factor for T2D independently of other FINDRISC factors (odds ratio (OR) 2.5, 95% CI 1.6-3.9). The FINDRISC algorithm predicted that more Iraqis than Swedes (16.2 vs. 12.3%, p < 0.001) will develop T2D within the next decade. The total annual costs for excess T2D risk in Iraqis are estimated to exceed 2.3 million euros in 2005, not accounting for worse quality of life. Conclusions: Our study suggests that Middle Eastern ethnicity should be considered an independent risk indicator for diabetes. Accordingly, the implementation of culturally tailored prevention programs may be warranted. (C) 2014 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

  • 15. Bennet, L.
    et al.
    Lindblad, U.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    A family history of diabetes determines poorer glycaemic control and younger age of diabetes onset in immigrants from the Middle East compared with native Swedes2015Ingår i: Diabetes & Metabolism, ISSN 1262-3636, E-ISSN 1878-1780, Vol. 41, nr 1, s. 45-54Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims. - Immigrant populations from the Middle East develop diabetes earlier than indigenous European populations; however, the underlying etiology is poorly understood. This study looked at the risk factors associated with early diabetes onset and, in non-diabetics, glycaemic control in immigrants from Iraq compared with native Swedes.

    Methods. - This cross-sectional population-based study comprised 1398 Iraqi immigrants and 757 Swedes (ages 30-75 years) residing in the same area of Malmo, Sweden. Outcomes were age at diabetes onset and glycaemic control (HbA(1c)) as assessed by Cox proportional hazards and linear regression, respectively.

    Results. - In Iraqis vs Swedes, clustering in the family history (in two or more relatives) was more prevalent (23.2% vs 3.6%, P<0.001) and diabetes onset occurred earlier (47.6 years vs 53.4 years, P=0.001). Having an Iraqi background independently raised the hazard ratio (HR) for diabetes onset. Diabetes risk due to family history was augmented by obesity, with the highest HRs observed in obese participants with clustering in the family history (HR: 5.1, 95% CI: 3.2-8.2) after adjusting for country of birth and gender. In participants without previously diagnosed diabetes (Iraqis: n=1270; Swedes: n=728), HbA(1c), levels were slightly higher in Iraqis than in Swedes (4.5% vs 4.4%, P=0.038). This difference was explained primarily by clustering in the family history rather than age, obesity, lifestyle or socioeconomic status.

    Conclusion. - The study shows that the greater predisposition to diabetes in Middle Eastern immigrants may be explained by a more extensive family history of the disorder; clinical interventions tailored to Middle Eastern immigrants with such a family history are thus warranted.

  • 16. Bennet, Louise
    et al.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden; Department of Diabetes and Endocrinology/Lund University Diabetes Centre, Skåne University Hospital, Malmö, Sweden; Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
    Zöller, Bengt
    Groop, Leif
    Family history of diabetes and its relationship with insulin secretion and insulin sensitivity in Iraqi immigrants and native Swedes: a population-based cohort study2018Ingår i: Acta Diabetologica, ISSN 0940-5429, E-ISSN 1432-5233, Vol. 55, nr 3, s. 233-242Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims Middle Eastern immigrants to western countries are at high risk of developing type 2 diabetes. However, the heritability and impact of rst-degree family history (FH) of type 2 diabetes on insulin secretion and action have not been adequately described. Methods Citizens of Malmö, Sweden, aged 30–75 years born in Iraq or Sweden were invited to participate in this population- based study. Insulin secretion (corrected insulin response and oral disposition index) and action (insulin sensitivity index) were assessed by oral glucose tolerance tests.

    Results In total, 45.7% of Iraqis (616/1348) and 27.4% of native Swedes (201/733) had FH in parent(s), sibling(s) or single parent and sibling, i.e., FH+. Approximately 8% of Iraqis and 0.7% of Swedes had ≥ 3 sibling(s) and parent(s) with diabetes, i.e., FH++. Irrespective of family size, prediabetes and diabetes increased with family burden (FH− 29.4%; FH+ 38.8%; FH++ 61.7%) without signi cant di erences across ethnicities. With increasing level of family burden, insulin secretion rather than insulin action decreased. Individuals with a combination of ≥ 3 siblings and parents with diabetes presented with the lowest levels of insulin secretion.

    Conclusions The Iraqi immigrant population often present with a strong familial burden of type 2 diabetes with the worst glycemic control and highest diabetes risk in individuals with ≥ 3 siblings and parents with diabetes. Our data show that in a population still free from diabetes familial burden in uences insulin secretion to a higher degree than insulin action and may be a logical target for intervention. 

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  • 17. Bennet, Louise
    et al.
    Groop, Leif
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Nutrition, Harvard School of Public Health, Boston, MA, USA; Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden; Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Malmö, Sweden.
    Country of birth modifies the association of fatty liver index with insulin action in Middle Eastern immigrants to Sweden2015Ingår i: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 110, nr 1, s. 66-74Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims: Non-alcohol fatty liver disease (NAFLD) is a strong risk factor for insulin resistance and type 2 diabetes. The prevalence of NAFLD varies across populations of different ethnic backgrounds but the prevalence in Middle Eastern populations, which are at high risk of type 2 diabetes, is largely unknown. Using fatty liver index (FLI) as a proxy for NAFLD the aim was to calculate the odds of NAFLD (FLI >= 70) given country of origin and further to investigate the associations between ISI and FLI. Methods: In 2010-2012 we conducted a population-based study of individuals aged 30-75 years born in Iraq or Sweden, in whom anthropometrics, fasting blood samples and oral glucose tolerance tests were performed and sociodemography and lifestyle behaviors characterized. Results: A higher proportion of Iraqis (N = 1085) than Swedes (N = 605) had a high probability of NAFLD (FLI >= 70, 32.5 vs. 22.6%, p < 0.001, age-and sex-adjusted data) and ISI was more severely impaired (70.7 vs. 95.9%, p < 0.001). Independently of traditional risk factors for NAFLD, being born in Iraqi increased the risk of FLI >= 70 (OR 1.59: 95% CI 1.15, 2.20). Furthermore, country of birth presented a stronger association between ISI and FLI >= 70 in Iraqis than in Swedes (P-interaction = 0.019). Conclusions: Our data indicate that immigrants from Iraq are at higher risk of NAFLD. The finding that country of birth modifies the relationship of FLI with ISI, suggests that liver fat may be a stronger determinant of impaired insulin action and increased risk of type 2 diabetes in Iraqis than in Swedes.

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  • 18. Bennet, Louise
    et al.
    Groop, Leif
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Ethnic differences in the contribution of insulin action and secretion to type 2 diabetes in immigrants from the Middle East compared to native Swedes2014Ingår i: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 105, nr 1, s. 79-87Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims: We investigated insulin action (insulin sensitivity index, ISI) and insulin secretion (oral disposition indices, DIo) and studied metabolic, demographic and lifestyle-related risk factors for type 2 diabetes and insulin action, in the largest non-European immigrant group to Sweden, immigrants from Iraq and native Swedes.

    Methods: Population-based, cross-sectional study conducted 2010-2012 including residents 30-75 years of age born in Iraq or Sweden, in whom oral glucose tolerance tests were performed and sociodemography and lifestyle behaviors were characterized.

    Results: In Iraqis compared to Swedes, ISI was more impaired (76.9 vs. 102.3, p < .001) whereas corrected insulin response CIR was higher (226.6 vs. 188.6, p = .016). However, insulin secretion was inadequate given the substantial insulin resistance, as indicated by lower DIo indices in Iraqis than in Swedes (DIo 12,712.9 vs. 14,659.2, p < .001). The crude ethnic difference in ISI was not offset by traditional risk factors like waist circumference, body mass index or family history of diabetes. In Iraqis, ISI conveyed somewhat higher odds of type 2 diabetes than in Swedes (odds ratio OR 0.98, 95% CI 0.97-0.99) vs. OR 0.95, 0.92-0.99), as indicated by an interaction between country of birth and ISI (P-interaction = .044).

    Conclusion: This study reports ethnic differences in the contribution of insulin action to type 2 diabetes. Our data suggests that the impaired insulin action observed in immigrants from the Middle East to Sweden is not fully explained by established risk factors.

    (C) 2014 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

  • 19. Bentley, Amy R.
    et al.
    Sung, Yun J.
    Brown, Michael R.
    Winkler, Thomas W.
    Kraja, Aldi T.
    Ntalla, Ioanna
    Schwander, Karen
    Chasman, Daniel, I
    Lim, Elise
    Deng, Xuan
    Guo, Xiuqing
    Liu, Jingmin
    Lu, Yingchang
    Cheng, Ching-Yu
    Sim, Xueling
    Vojinovic, Dina
    Huffman, Jennifer E.
    Musani, Solomon K.
    Li, Changwei
    Feitosa, Mary F.
    Richard, Melissa A.
    Noordam, Raymond
    Baker, Jenna
    Chen, Guanjie
    Aschard, Hugues
    Bartz, Traci M.
    Ding, Jingzhong
    Dorajoo, Rajkumar
    Manning, Alisa K.
    Rankinen, Tuomo
    Smith, Albert, V
    Tajuddin, Salman M.
    Zhao, Wei
    Graff, Mariaelisa
    Alver, Maris
    Boissel, Mathilde
    Chai, Jin Fang
    Chen, Xu
    Divers, Jasmin
    Evangelou, Evangelos
    Gao, Chuan
    Goel, Anuj
    Hagemeijer, Yanick
    Harris, Sarah E.
    Hartwig, Fernando P.
    He, Meian
    Horimoto, Andrea R. V. R.
    Hsu, Fang-Chi
    Hung, Yi-Jen
    Jackson, Anne U.
    Kasturiratne, Anuradhani
    Komulainen, Pirjo
    Kuehnel, Brigitte
    Leander, Karin
    Lin, Keng-Hung
    Luan, Jian'an
    Lyytikainen, Leo-Pekka
    Matoba, Nana
    Nolte, Ilja M.
    Pietzner, Maik
    Prins, Bram
    Riaz, Muhammad
    Robino, Antonietta
    Said, M. Abdullah
    Schupf, Nicole
    Scott, Robert A.
    Sofer, Tamar
    Stancakova, Alena
    Takeuchi, Fumihiko
    Tayo, Bamidele O.
    van der Most, Peter J.
    Varga, Tibor V.
    Wang, Tzung-Dau
    Wang, Yajuan
    Ware, Erin B.
    Wen, Wanqing
    Xiang, Yong-Bing
    Yanek, Lisa R.
    Zhang, Weihua
    Zhao, Jing Hua
    Adeyemo, Adebowale
    Afaq, Saima
    Amin, Najaf
    Amini, Marzyeh
    Arking, Dan E.
    Arzumanyan, Zorayr
    Aung, Tin
    Ballantyne, Christie
    Barr, R. Graham
    Bielak, Lawrence F.
    Boerwinkle, Eric
    Bottinger, Erwin P.
    Broeckel, Ulrich
    Brown, Morris
    Cade, Brian E.
    Campbell, Archie
    Canouil, Mickael
    Charumathi, Sabanayagam
    Chen, Yii-Der Ida
    Christensen, Kaare
    Concas, Maria Pina
    Connell, John M.
    de las Fuentes, Lisa
    de Silva, H. Janaka
    de Vries, Paul S.
    Doumatey, Ayo
    Duan, Qing
    Eaton, Charles B.
    Eppinga, Ruben N.
    Faul, Jessica D.
    Floyd, James S.
    Forouhi, Nita G.
    Forrester, Terrence
    Friedlander, Yechiel
    Gandin, Ilaria
    Gao, He
    Ghanbari, Mohsen
    Gharib, Sina A.
    Gigante, Bruna
    Giulianini, Franco
    Grabe, Hans J.
    Gu, C. Charles
    Harris, Tamara B.
    Heikkinen, Sami
    Heng, Chew-Kiat
    Hirata, Makoto
    Hixson, James E.
    Ikram, M. Arfan
    Jia, Yucheng
    Joehanes, Roby
    Johnson, Craig
    Jonas, Jost Bruno
    Justice, Anne E.
    Katsuya, Tomohiro
    Khor, Chiea Chuen
    Kilpelainen, Tuomas O.
    Koh, Woon-Puay
    Kolcic, Ivana
    Kooperberg, Charles
    Krieger, Jose E.
    Kritchevsky, Stephen B.
    Kubo, Michiaki
    Kuusisto, Johanna
    Lakka, Timo A.
    Langefeld, Carl D.
    Langenberg, Claudia
    Launer, Lenore J.
    Lehne, Benjamin
    Lewis, Cora E.
    Li, Yize
    Liang, Jingjing
    Lin, Shiow
    Liu, Ching-Ti
    Liu, Jianjun
    Liu, Kiang
    Loh, Marie
    Lohman, Kurt K.
    Louie, Tin
    Luzzi, Anna
    Magi, Reedik
    Mahajan, Anubha
    Manichaikul, Ani W.
    McKenzie, Colin A.
    Meitinger, Thomas
    Metspalu, Andres
    Milaneschi, Yuri
    Milani, Lili
    Mohlke, Karen L.
    Momozawa, Yukihide
    Morris, Andrew P.
    Murray, Alison D.
    Nalls, Mike A.
    Nauck, Matthias
    Nelson, Christopher P.
    North, Kari E.
    O'Connell, Jeffrey R.
    Palmer, Nicholette D.
    Papanicolau, George J.
    Pedersen, Nancy L.
    Peters, Annette
    Peyser, Patricia A.
    Polasek, Ozren
    Poulter, Neil
    Raitakari, Olli T.
    Reiner, Alex P.
    Renstrom, Frida
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Skåne University Hospital, Malmö, Sweden.
    Rice, Treva K.
    Rich, Stephen S.
    Robinson, Jennifer G.
    Rose, Lynda M.
    Rosendaal, Frits R.
    Rudan, Igor
    Schmidt, Carsten O.
    Schreiner, Pamela J.
    Scott, William R.
    Sever, Peter
    Shi, Yuan
    Sidney, Stephen
    Sims, Mario
    Smith, Jennifer A.
    Snieder, Harold
    Starr, John M.
    Strauch, Konstantin
    Stringham, Heather M.
    Tan, Nicholas Y. Q.
    Tang, Hua
    Taylor, Kent D.
    Teo, Yik Ying
    Tham, Yih Chung
    Tiemeier, Henning
    Turner, Stephen T.
    Uitterlinden, Andre G.
    van Heemst, Diana
    Waldenberger, Melanie
    Wang, Heming
    Wang, Lan
    Wang, Lihua
    Wei, Wen Bin
    Williams, Christine A.
    Wilson, Gregory, Sr.
    Wojczynski, Mary K.
    Yao, Jie
    Young, Kristin
    Yu, Caizheng
    Yuan, Jian-Min
    Zhou, Jie
    Zonderman, Alan B.
    Becker, Diane M.
    Boehnke, Michael
    Bowden, Donald W.
    Chambers, John C.
    Cooper, Richard S.
    de Faire, Ulf
    Deary, Ian J.
    Elliott, Paul
    Esko, Tonu
    Farrall, Martin
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Return to work after interdisciplinary pain rehabilitation Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan; Department of Nutrition, Harvard T. H. Chan School of Public Health, Harvard University, Boston, MA, USA; OCDEM, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
    Freedman, Barry, I
    Froguel, Philippe
    Gasparini, Paolo
    Gieger, Christian
    Horta, Bernardo L.
    Juang, Jyh-Ming Jimmy
    Kamatani, Yoichiro
    Kammerer, Candace M.
    Kato, Norihiro
    Kooner, Jaspal S.
    Laakso, Markku
    Laurie, Cathy C.
    Lee, I-Te
    Lehtimaki, Terho
    Magnusson, Patrik K. E.
    Oldehinkel, Albertine J.
    Penninx, Brenda W. J. H.
    Pereira, Alexandre C.
    Rauramaa, Rainer
    Redline, Susan
    Samani, Nilesh J.
    Scott, James
    Shu, Xiao-Ou
    van der Harst, Pim
    Wagenknecht, Lynne E.
    Wang, Jun-Sing
    Wang, Ya Xing
    Wareham, Nicholas J.
    Watkins, Hugh
    Weir, David R.
    Wickremasinghe, Ananda R.
    Wu, Tangchun
    Zeggini, Eleftheria
    Zheng, Wei
    Bouchard, Claude
    Evans, Michele K.
    Gudnason, Vilmundur
    Kardia, Sharon L. R.
    Liu, Yongmei
    Psaty, Bruce M.
    Ridker, Paul M.
    van Dam, Rob M.
    Mook-Kanamori, Dennis O.
    Fornage, Myriam
    Province, Michael A.
    Kelly, Tanika N.
    Fox, Ervin R.
    Hayward, Caroline
    van Duijn, Cornelia M.
    Tai, E. Shyong
    Wong, Tien Yin
    Loos, Ruth J. F.
    Franceschini, Nora
    Rotter, Jerome, I
    Zhu, Xiaofeng
    Bierut, Laura J.
    Gauderman, W. James
    Rice, Kenneth
    Munroe, Patricia B.
    Morrison, Alanna C.
    Rao, Dabeeru C.
    Rotimi, Charles N.
    Cupples, L. Adrienne
    Multi-ancestry genome-wide gene-smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids2019Ingår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 51, nr 4, s. 636-+Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The concentrations of high- and low-density-lipoprotein cholesterol and triglycerides are influenced by smoking, but it is unknown whether genetic associations with lipids may be modified by smoking. We conducted a multi-ancestry genome-wide gene-smoking interaction study in 133,805 individuals with follow-up in an additional 253,467 individuals. Combined meta-analyses identified 13 new loci associated with lipids, some of which were detected only because association differed by smoking status. Additionally, we demonstrate the importance of including diverse populations, particularly in studies of interactions with lifestyle factors, where genomic and lifestyle differences by ancestry may contribute to novel findings.

  • 20. Berndt, Sonja I.
    et al.
    Gustafsson, Stefan
    Maegi, Reedik
    Ganna, Andrea
    Wheeler, Eleanor
    Feitosa, Mary F.
    Justice, Anne E.
    Monda, Keri L.
    Croteau-Chonka, Damien C.
    Day, Felix R.
    Esko, Tonu
    Fall, Tove
    Ferreira, Teresa
    Gentilini, Davide
    Jackson, Anne U.
    Luan, Jian'an
    Randall, Joshua C.
    Vedantam, Sailaja
    Willer, Cristen J.
    Winkler, Thomas W.
    Wood, Andrew R.
    Workalemahu, Tsegaselassie
    Hu, Yi-Juan
    Lee, Sang Hong
    Liang, Liming
    Lin, Dan-Yu
    Min, Josine L.
    Neale, Benjamin M.
    Thorleifsson, Gudmar
    Yang, Jian
    Albrecht, Eva
    Amin, Najaf
    Bragg-Gresham, Jennifer L.
    Cadby, Gemma
    den Heijer, Martin
    Eklund, Niina
    Fischer, Krista
    Goel, Anuj
    Hottenga, Jouke-Jan
    Huffman, Jennifer E.
    Jarick, Ivonne
    Johansson, Asa
    Johnson, Toby
    Kanoni, Stavroula
    Kleber, Marcus E.
    Koenig, Inke R.
    Kristiansson, Kati
    Kutalik, Zoltn
    Lamina, Claudia
    Lecoeur, Cecile
    Li, Guo
    Mangino, Massimo
    McArdle, Wendy L.
    Medina-Gomez, Carolina
    Mueller-Nurasyid, Martina
    Ngwa, Julius S.
    Nolte, Ilja M.
    Paternoster, Lavinia
    Pechlivanis, Sonali
    Perola, Markus
    Peters, Marjolein J.
    Preuss, Michael
    Rose, Lynda M.
    Shi, Jianxin
    Shungin, Dmitry
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Smith, Albert Vernon
    Strawbridge, Rona J.
    Surakka, Ida
    Teumer, Alexander
    Trip, Mieke D.
    Tyrer, Jonathan
    Van Vliet-Ostaptchouk, Jana V.
    Vandenput, Liesbeth
    Waite, Lindsay L.
    Zhao, Jing Hua
    Absher, Devin
    Asselbergs, Folkert W.
    Atalay, Mustafa
    Attwood, Antony P.
    Balmforth, Anthony J.
    Basart, Hanneke
    Beilby, John
    Bonnycastle, Lori L.
    Brambilla, Paolo
    Bruinenberg, Marcel
    Campbell, Harry
    Chasman, Daniel I.
    Chines, Peter S.
    Collins, Francis S.
    Connell, John M.
    Cookson, William O.
    de Faire, Ulf
    de Vegt, Femmie
    Dei, Mariano
    Dimitriou, Maria
    Edkins, Sarah
    Estrada, Karol
    Evans, David M.
    Farrall, Martin
    Ferrario, Marco M.
    Ferrieres, Jean
    Franke, Lude
    Frau, Francesca
    Gejman, Pablo V.
    Grallert, Harald
    Groenberg, Henrik
    Gudnason, Vilmundur
    Hall, Alistair S.
    Hall, Per
    Hartikainen, Anna-Liisa
    Hayward, Caroline
    Heard-Costa, Nancy L.
    Heath, Andrew C.
    Hebebrand, Johannes
    Homuth, Georg
    Hu, Frank B.
    Hunt, Sarah E.
    Hyppoenen, Elina
    Iribarren, Carlos
    Jacobs, Kevin B.
    Jansson, John-Olov
    Jula, Antti
    Kahonen, Mika
    Kathiresan, Sekar
    Kee, Frank
    Khaw, Kay-Tee
    Kivimaki, Mika
    Koenig, Wolfgang
    Kraja, Aldi T.
    Kumari, Meena
    Kuulasmaa, Kari
    Kuusisto, Johanna
    Laitinen, Jaana H.
    Lakka, Timo A.
    Langenberg, Claudia
    Launer, Lenore J.
    Lind, Lars
    Lindstrom, Jaana
    Liu, Jianjun
    Liuzzi, Antonio
    Lokki, Marja-Liisa
    Lorentzon, Mattias
    Madden, Pamela A.
    Magnusson, Patrik K.
    Manunta, Paolo
    Marek, Diana
    Maerz, Winfried
    Leach, Irene Mateo
    McKnight, Barbara
    Medland, Sarah E.
    Mihailov, Evelin
    Milani, Lili
    Montgomery, Grant W.
    Mooser, Vincent
    Muehleisen, Thomas W.
    Munroe, Patricia B.
    Musk, Arthur W.
    Narisu, Narisu
    Navis, Gerjan
    Nicholson, George
    Nohr, Ellen A.
    Ong, Ken K.
    Oostra, Ben A.
    Palmer, Colin N. A.
    Palotie, Aarno
    Peden, John F.
    Pedersen, Nancy
    Peters, Annette
    Polasek, Ozren
    Pouta, Anneli
    Pramstaller, Peter P.
    Prokopenko, Inga
    Puetter, Carolin
    Radhakrishnan, Aparna
    Raitakari, Olli
    Rendon, Augusto
    Rivadeneira, Fernando
    Rudan, Igor
    Saaristo, Timo E.
    Sambrook, Jennifer G.
    Sanders, Alan R.
    Sanna, Serena
    Saramies, Jouko
    Schipf, Sabine
    Schreiber, Stefan
    Schunkert, Heribert
    Shin, So-Youn
    Signorini, Stefano
    Sinisalo, Juha
    Skrobek, Boris
    Soranzo, Nicole
    Stancakova, Alena
    Stark, Klaus
    Stephens, Jonathan C.
    Stirrups, Kathleen
    Stolk, Ronald P.
    Stumvoll, Michael
    Swift, Amy J.
    Theodoraki, Eirini V.
    Thorand, Barbara
    Tregouet, David-Alexandre
    Tremoli, Elena
    Van der Klauw, Melanie M.
    van Meurs, Joyce B. J.
    Vermeulen, Sita H.
    Viikari, Jorma
    Virtamo, Jarmo
    Vitart, Veronique
    Waeber, Gerard
    Wang, Zhaoming
    Widen, Elisabeth
    Wild, Sarah H.
    Willemsen, Gonneke
    Winkelmann, Bernhard R.
    Witteman, Jacqueline C. M.
    Wolffenbuttel, Bruce H. R.
    Wong, Andrew
    Wright, Alan F.
    Zillikens, M. Carola
    Amouyel, Philippe
    Boehm, Bernhard O.
    Boerwinkle, Eric
    Boomsma, Dorret I.
    Caulfield, Mark J.
    Chanock, Stephen J.
    Cupples, L. Adrienne
    Cusi, Daniele
    Dedoussis, George V.
    Erdmann, Jeanette
    Eriksson, Johan G.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Froguel, Philippe
    Gieger, Christian
    Gyllensten, Ulf
    Hamsten, Anders
    Harris, Tamara B.
    Hengstenberg, Christian
    Hicks, Andrew A.
    Hingorani, Aroon
    Hinney, Anke
    Hofman, Albert
    Hovingh, Kees G.
    Hveem, Kristian
    Illig, Thomas
    Jarvelin, Marjo-Riitta
    Joeckel, Karl-Heinz
    Keinanen-Kiukaanniemi, Sirkka M.
    Kiemeney, Lambertus A.
    Kuh, Diana
    Laakso, Markku
    Lehtimaki, Terho
    Levinson, Douglas F.
    Martin, Nicholas G.
    Metspalu, Andres
    Morris, Andrew D.
    Nieminen, Markku S.
    Njolstad, Inger
    Ohlsson, Claes
    Oldehinkel, Albertine J.
    Ouwehand, Willem H.
    Palmer, Lyle J.
    Penninx, Brenda
    Power, Chris
    Province, Michael A.
    Psaty, Bruce M.
    Qi, Lu
    Rauramaa, Rainer
    Ridker, Paul M.
    Ripatti, Samuli
    Salomaa, Veikko
    Samani, Nilesh J.
    Snieder, Harold
    Sorensen, Thorkild I. A.
    Spector, Timothy D.
    Stefansson, Kari
    Tonjes, Anke
    Tuomilehto, Jaakko
    Uitterlinden, Andre G.
    Uusitupa, Matti
    van der Harst, Pim
    Vollenweider, Peter
    Wallaschofski, Henri
    Wareham, Nicholas J.
    Watkins, Hugh
    Wichmann, H-Erich
    Wilson, James F.
    Abecasis, Goncalo R.
    Assimes, Themistocles L.
    Barroso, Ines
    Boehnke, Michael
    Borecki, Ingrid B.
    Deloukas, Panos
    Fox, Caroline S.
    Frayling, Timothy
    Groop, Leif C.
    Haritunian, Talin
    Heid, Iris M.
    Hunter, David
    Kaplan, Robert C.
    Karpe, Fredrik
    Moffatt, Miriam F.
    Mohlke, Karen L.
    O'Connell, Jeffrey R.
    Pawitan, Yudi
    Schadt, Eric E.
    Schlessinger, David
    Steinthorsdottir, Valgerdur
    Strachan, David P.
    Thorsteinsdottir, Unnur
    van Duijn, Cornelia M.
    Visscher, Peter M.
    Di Blasio, Anna Maria
    Hirschhorn, Joel N.
    Lindgren, Cecilia M.
    Morris, Andrew P.
    Meyre, David
    Scherag, Andr
    McCarthy, Mark I.
    Speliotes, Elizabeth K.
    North, Kari E.
    Loos, Ruth J. F.
    Ingelsson, Erik
    Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture2013Ingår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 45, nr 5, s. 501-U69Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

  • 21. Brage, Sören
    et al.
    Brage, Niels
    Ekelund, Ulf
    Luan, Jian'an
    Franks, Paul
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Froberg, Karsten
    Wareham, Nicholas J
    Effect of combined movement and heart rate monitor placement on physical activity estimates during treadmill locomotion and free-living.2006Ingår i: Eur J Appl Physiol, ISSN 1439-6319, Vol. 96, nr 5, s. 517-24Artikel i tidskrift (Refereegranskat)
  • 22. Brage, Søren
    et al.
    Ekelund, Ulf
    Brage, Niels
    Hennings, Mark A
    Froberg, Karsten
    Franks, Paul
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Wareham, Nicholas J
    Hierarchy of individual calibration levels for heart rate and accelerometry to measure physical activity.2007Ingår i: J Appl Physiol, ISSN 8750-7587, Vol. 103, nr 2, s. 682-92Artikel i tidskrift (Refereegranskat)
  • 23. Brand, J. S.
    et al.
    Onland-Moret, N. C.
    Eijkemans, M. J. C.
    Tjonneland, A.
    Roswall, N.
    Overvad, K.
    Fagherazzi, G.
    Clavel-Chapelon, F.
    Dossus, L.
    Lukanova, Annekatrin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap. Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg.
    Grote, V.
    Bergmann, M. M.
    Boeing, H.
    Trichopoulou, A.
    Tzivoglou, M.
    Trichopoulos, D.
    Grioni, S.
    Mattiello, A.
    Masala, G.
    Tumino, R.
    Vineis, P.
    Bueno-de-Mesquita, H. B.
    Weiderpass, E.
    Redondo, M. L.
    Sanchez, M. J.
    Castano, J. M. Huerta
    Arriola, L.
    Ardanaz, E.
    Duell, E. J.
    Rolandsson, O.
    Franks, P. W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Butt, S.
    Nilsson, P.
    Khaw, K. T.
    Wareham, N.
    Travis, R.
    Romieu, I.
    Gunter, M. J.
    Riboli, E.
    van der Schouw, Y. T.
    Diabetes and Onset of Natural Menopause: Results From the European Prospective Investigation Into Cancer and Nutrition EDITORIAL COMMENT2015Ingår i: Obstetrical and Gynecological Survey, ISSN 0029-7828, E-ISSN 1533-9866, Vol. 70, nr 8, s. 507-508Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    The age at natural menopause (ANM) in the Western world ranges from 40 to 60 years, with an average onset of 51 years. The exact mechanisms underlying the timing of ANM are not completely understood. Both genetic and environmental factors are involved. The best-established environmental factor affecting ANM is smoking; menopause occurs 1 to 2 years earlier in smokers. In addition to genetic and environmental factors, chronic metabolic diseases may influence ANM. Some evidence suggests that diabetes may accelerate menopausal onset. With more women of childbearing age receiving a diagnosis of diabetes, it is important to examine the impact of diabetes on reproductive health. This study was designed to determine whether ANM occurs at an earlier age among women who have diabetes before menopause than in women without diabetes. Data were obtained from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a large multicenter prospective cohort study investigating the relationship between diet, lifestyle, and genetic factors and the incidence of cancer and other chronic diseases. A cohort of 519,978 men and women, mostly aged 27 to 70 years, were recruited primarily from the general population between 1992 and 2000. A total of 367,331 women participated in the EPIC study. After exclusions, 258,898 of these women met study inclusion criteria. Diabetes status at baseline and menopausal age were based on self-report and were obtained through questionnaires. Participants were asked if they had ever been diagnosed with diabetes and if so at what age. Associations of diabetes and age at diabetes diagnosis with ANM were estimated using time-dependent Cox regression analyses, with stratification by center and adjustments for age, smoking, reproductive, and known diabetes risk factors including smoking and with age from birth to menopause or censoring as the underlying time scale. Overall, there was no statistically significant lower risk of becoming menopausal among women with diabetes than women with no diabetes; the hazard ratio (HR) was 0.94, with a 95% confidence interval (CI) of 0.89 to 1.01. However, compared with women with no diabetes, women with diabetes before the age of 20 years had an earlier menopause (10-20 years [HR, 1.43; 95% CI, 1.02-2.01] and <10 years [HR, 1.59; 95% CI, 1.03-2.43]), whereas women with diabetes at age 50 years or older had a later menopause (HR, 0.81; 95% CI, 0.70-0.95). No association with ANM was found for diabetes onset between the ages 20 and 50 years. Strengths of the study include its large sample size and the measurement of a broad set of potential confounders. However, there were several limitations. First, results may have been underestimated because of survival bias. Second, the sequence of menopause and diabetes in women with a late age at diabetes is uncertain, as both events occur in a short period, and both diabetes and menopause status were based on self-report, not verified by medical records. Third, no distinction was made between types 1 and 2 diabetes. Although there is no overall association between diabetes and age at menopause, the data suggest that early-onset diabetes may accelerate menopause. The delaying effect of late-onset diabetes on ANM is not in agreement with other studies suggesting the opposite association.

  • 24.
    Brand, J. S.
    et al.
    Utrecht, The Netherlands.
    Onland-Moret, N. C.
    Utrecht, The Netherlands.
    Eijkemans, M. J. C.
    Utrecht, The Netherlands.
    Tjönneland, A.
    Copenhagen, Denmark .
    Roswall, N.
    Copenhagen, Denmark .
    Overvad, K.
    Aarhus, Denmark .
    Fagherazzi, G.
    Villejuif, France.
    Clavel-Chapelon, F.
    Villejuif, France.
    Dossus, L.
    Villejuif, France.
    Lukanova, Annekatrin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap. Heidelberg, Germany .
    Grote, V.
    Heidelberg, Germany .
    Bergmann, M. M.
    Potsdam, Germany.
    Boeing, H.
    Potsdam, Germany.
    Trichopoulou, A.
    Athens, Greece.
    Tzivoglou, M.
    Athens, Greece.
    Trichopoulos, D.
    Athens, Greece; Boston, MA 02115, USA.
    Grioni, S.
    Milan, Italy.
    Mattiello, A.
    Naples, Italy.
    Masala, G.
    Florence, Italy.
    Tumino, R.
    Ragusa, Italy.
    Vineis, P.
    Torino, Italy; London, UK.
    Bueno-De-Mesquita, H. B.
    The Netherlands; London, United Kingdom; Kuala Lumpur, Malaysia .
    Weiderpass, E.
    Norway; Stockholm, Sweden; Helsinki, Finland .
    Redondo, M. L.
    Asturias, Spain.
    Sanchez, M. J.
    Spain.
    Huerta Castano, J. M.
    Spain.
    Arriola, L.
    San Sebastian, Spain.
    Ardanaz, E.
    Spain.
    Duell, E. J.
    Barcelona, Spain.
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Franks, Paul
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Malmö, Sweden.
    Butt, S.
    Malmö, Sweden.
    Nilsson, P.
    Malmö, Sweden.
    Khaw, K. T.
    Cambridge, UK.
    Wareham, N.
    Cambridge, UK.
    Travis, R.
    Oxford, UK.
    Romieu, I.
    Lyon, France.
    Gunter, M. J.
    London, UK .
    Riboli, E.
    London, UK .
    van der Schouw, Y. T.
    Utrecht, The Netherlands.
    Diabetes and onset of natural menopause: results from the European Prospective Investigation into Cancer and Nutrition2015Ingår i: Human Reproduction, ISSN 0268-1161, E-ISSN 1460-2350, Vol. 30, nr 6, s. 1491-1498Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    STUDY QUESTION: Do women who have diabetes before menopause have their menopause at an earlier age compared with women without diabetes? SUMMARY ANSWER: Although there was no overall association between diabetes and age at menopause, our study suggests that early-onset diabetes may accelerate menopause. WHAT IS KNOWN ALREADY: Today, more women of childbearing age are being diagnosed with diabetes, but little is known about the impact of diabetes on reproductive health. STUDY DESIGN, SIZE, DURATION: We investigated the impact of diabetes on age at natural menopause (ANM) in 258 898 women from the European Prospective Investigation into Cancer and Nutrition (EPIC), enrolled between 1992 and 2000. PARTICIPANTS/MATERIALS, SETTING, METHODS: Determinant and outcome information was obtained through questionnaires. Time-dependent Cox regression analyses were used to estimate the associations of diabetes and age at diabetes diagnosis with ANM, stratified by center and adjusted for age, smoking, reproductive and diabetes risk factors and with age from birth to menopause or censoring as the underlying time scale. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, no association between diabetes and ANM was found (hazard ratio (HR) = 0.94; 95% confidence interval (CI) 0.89-1.01). However, women with diabetes before the age of 20 years had an earlier menopause (10-20 years: HR = 1.43; 95% CI 1.02-2.01, <10 years: HR = 1.59; 95% CI 1.03-2.43) compared with non-diabetic women, whereas women with diabetes at age 50 years and older had a later menopause (HR = 0.81; 95% CI 0.70-0.95). None of the other age groups were associated with ANM. LIMITATIONS, REASONS FOR CAUTION: Strengths of the study include the large sample size and the broad set of potential confounders measured. However, results may have been underestimated due to survival bias. We cannot be sure about the sequence of the events in women with a late age at diabetes, as both events then occur in a short period. We could not distinguish between type 1 and type 2 diabetes. WIDER IMPLICATIONS OF THE FINDINGS: Based on the literature, an accelerating effect of early-onset diabetes on ANM might be plausible. A delaying effect of late-onset diabetes on ANM has not been reported before, and is not in agreement with recent studies suggesting the opposite association.

  • 25. Brand, Judith S.
    et al.
    van der Schouw, Yvonne T.
    Onland-Moret, N. Charlotte
    Sharp, Stephen J.
    Ong, Ken K.
    Khaw, Kay-Tee
    Ardanaz, Eva
    Amiano, Pilar
    Boeing, Heiner
    Chirlaque, Maria-Dolores
    Clavel-Chapelon, Francoise
    Crowe, Francesca L.
    de Lauzon-Guillain, Blandine
    Duell, Eric J.
    Fagherazzi, Guy
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Grioni, Sara
    Groop, Leif C.
    Kaaks, Rudolf
    Key, Timothy J.
    Nilsson, Peter M.
    Overvad, Kim
    Palli, Domenico
    Panico, Salvatore
    Quiros, J. Ramon
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Sacerdote, Carlotta
    Sanchez, Maria-Jose
    Slimani, Nadia
    Teucher, Birgit
    Tjonneland, Anne
    Tumino, Rosario
    van der A, Daphne L.
    Feskens, Edith J. M.
    Langenberg, Claudia
    Forouhi, Nita G.
    Riboli, Elio
    Wareham, Nicholas J.
    Age at Menopause, Reproductive Life Span, and Type 2 Diabetes Risk2013Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 36, nr 4, s. 1012-1019Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE-Age at menopause is an important determinant of future health outcomes, but little is known about its relationship with type 2 diabetes. We examined the associations of menopausal age and reproductive life span (menopausal age minus menarcheal age) with diabetes risk.

    RESEARCH DESIGN AND METHODS-Data were obtained from the InterAct study, a prospective case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition. A total of 3,691 postmenopausal type 2 diabetic case subjects and 4,408 subcohort members were included in the analysis, with a median follow-up of 11 years. Prentice weighted Cox proportional hazards models were adjusted for age, known risk factors for diabetes, and reproductive factors, and effect modification by BMI, waist circumference, and smoking was studied.

    RESULTS-Mean (SD) age of the subcohort was 59.2 (5.8) years. After multivariable adjustment, hazard ratios (HRs) of type 2 diabetes were 1.32 (95% CI 1.04-1.69), 1.09 (0.90-1.31), 0.97 (0.86-1.10), and 0.85 (0.70-1.03) for women with menopause at ages <40, 40-44, 45-49, and >= 55 years, respectively, relative to those with menopause at age 50-54 years. The HR per SD younger age at menopause was 1.08 (1.02-1.14). Similarly, a shorter reproductive life span was associated with a higher diabetes risk (HR per SD lower reproductive life span 1.06 [ 1.01-1.12]). No effect modification by BMI, waist circumference, or smoking was observed (P interaction all > 0.05).

    CONCLUSIONS-Early menopause is associated with a greater risk of type 2 diabetes. Diabetes Care 36:1012-1019, 2013

  • 26. Brazel, David M.
    et al.
    Jiang, Yu
    Hughey, Jordan M.
    Turcot, Valérie
    Zhan, Xiaowei
    Gong, Jian
    Batini, Chiara
    Weissenkampen, J. Dylan
    Liu, MengZhen
    Barnes, Daniel R.
    Bertelsen, Sarah
    Chou, Yi-Ling
    Erzurumluoglu, A. Mesut
    Faul, Jessica D.
    Haessler, Jeff
    Hammerschlag, Anke R.
    Hsu, Chris
    Kapoor, Manav
    Lai, Dongbing
    Le, Nhung
    de Leeuw, Christiaan A.
    Loukola, Anu
    Mangino, Massimo
    Melbourne, Carl A.
    Pistis, Giorgio
    Qaiser, Beenish
    Rohde, Rebecca
    Shao, Yaming
    Stringham, Heather
    Wetherill, Leah
    Zhao, Wei
    Agrawal, Arpana
    Bierut, Laura
    Chen, Chu
    Eaton, Charles B.
    Goate, Alison
    Haiman, Christopher
    Heath, Andrew
    Iacono, William G.
    Martin, Nicholas G.
    Polderman, Tinca J.
    Reiner, Alex
    Rice, John
    Schlessinger, David
    Scholte, H. Steven
    Smith, Jennifer A.
    Tardif, Jean-Claude
    Tindle, Hilary A.
    van der Leij, Andries R.
    Boehnke, Michael
    Chang-Claude, Jenny
    Cucca, Francesco
    David, Sean P.
    Foroud, Tatiana
    Howson, Joanna M. M.
    Kardia, Sharon L. R.
    Kooperberg, Charles
    Laakso, Markku
    Lettre, Guillaume
    Madden, Pamela
    McGue, Matt
    North, Kari
    Posthuma, Danielle
    Spector, Timothy
    Stram, Daniel
    Tobin, Martin D.
    Weir, David R.
    Kaprio, Jaakko
    Abecasis, Gonçalo R.
    Liu, Dajiang J.
    Vrieze, Scott
    Franks, Paul W. (Medarbetare/bidragsgivare)
    Exome Chip Meta-analysis Fine Maps Causal Variants and Elucidates the Genetic Architecture of Rare Coding Variants in Smoking and Alcohol Use2019Ingår i: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 85, nr 11, s. 946-955Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Smoking and alcohol use have been associated with common genetic variants in multiple loci. Rare variants within these loci hold promise in the identification of biological mechanisms in substance use. Exome arrays and genotype imputation can now efficiently genotype rare nonsynonymous and loss of function variants. Such variants are expected to have deleterious functional consequences and to contribute to disease risk.

    METHODS: We analyzed ∼250,000 rare variants from 16 independent studies genotyped with exome arrays and augmented this dataset with imputed data from the UK Biobank. Associations were tested for five phenotypes: cigarettes per day, pack-years, smoking initiation, age of smoking initiation, and alcoholic drinks per week. We conducted stratified heritability analyses, single-variant tests, and gene-based burden tests of nonsynonymous/loss-of-function coding variants. We performed a novel fine-mapping analysis to winnow the number of putative causal variants within associated loci.

    RESULTS: Meta-analytic sample sizes ranged from 152,348 to 433,216, depending on the phenotype. Rare coding variation explained 1.1% to 2.2% of phenotypic variance, reflecting 11% to 18% of the total single nucleotide polymorphism heritability of these phenotypes. We identified 171 genome-wide associated loci across all phenotypes. Fine mapping identified putative causal variants with double base-pair resolution at 24 of these loci, and between three and 10 variants for 65 loci. Twenty loci contained rare coding variants in the 95% credible intervals.

    CONCLUSIONS: Rare coding variation significantly contributes to the heritability of smoking and alcohol use. Fine-mapping genome-wide association study loci identifies specific variants contributing to the biological etiology of substance use behavior.

  • 27.
    Brito, Ema C
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Commentary on viewpoint: perspective on the future use of genomics in exercise prescription2008Ingår i: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 104, nr 4, s. 1248-1248Artikel i tidskrift (Övrigt vetenskapligt)
  • 28.
    Brito, Ema C
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lyssenko, V
    Renström, Frida
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Berglund, G
    Nilsson, PM
    Groop, L
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Previously associated type 2 diabetes variants may interact with physical activity to modify the risk of impaired glucose regulation and type 2 diabetes: a study of 16,003 Swedish adults2009Ingår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 58, nr 6, s. 1411-1418Artikel i tidskrift (Refereegranskat)
  • 29. Brunkwall, Louise
    et al.
    Chen, Yan
    Hindy, George
    Rukh, Gull
    Ericson, Ulrika
    Barroso, Ines
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, MA.
    Orho-Melander, Marju
    Renström, Frida
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Sugar-sweetened beverage consumption and genetic predisposition to obesity in 2 Swedish cohorts2016Ingår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 104, nr 3, s. 809-815Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The consumption of sugar-sweetened beverages (SSBs), which has increased substantially during the last decades, has been associated with obesity and weight gain.

    Objective: Common genetic susceptibility to obesity has been shown to modify the association between SSB intake and obesity risk in 3 prospective cohorts from the United States. We aimed to replicate these findings in 2 large Swedish cohorts.

    Design: Data were available for 21,824 healthy participants from the Malmö Diet and Cancer study and 4902 healthy participants from the Gene-Lifestyle Interactions and Complex Traits Involved in Elevated Disease Risk Study. Self-reported SSB intake was categorized into 4 levels (seldom, low, medium, and high). Unweighted and weighted genetic risk scores (GRSs) were constructed based on 30 body mass index [(BMI) in kg/m2]-associated loci, and effect modification was assessed in linear regression equations by modeling the product and marginal effects of the GRS and SSB intake adjusted for age-, sex-, and cohort-specific covariates, with BMI as the outcome. In a secondary analysis, models were additionally adjusted for putative confounders (total energy intake, alcohol consumption, smoking status, and physical activity).

    Results: In an inverse variance-weighted fixed-effects meta-analysis, each SSB intake category increment was associated with a 0.18 higher BMI (SE = 0.02; P = 1.7 × 10−20n = 26,726). In the fully adjusted model, a nominal significant interaction between SSB intake category and the unweighted GRS was observed (P-interaction = 0.03). Comparing the participants within the top and bottom quartiles of the GRS to each increment in SSB intake was associated with 0.24 (SE = 0.04; P = 2.9 × 10−8n = 6766) and 0.15 (SE = 0.04; P = 1.3 × 10−4n = 6835) higher BMIs, respectively.

    Conclusions: The interaction observed in the Swedish cohorts is similar in magnitude to the previous analysis in US cohorts and indicates that the relation of SSB intake and BMI is stronger in people genetically predisposed to obesity.

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  • 30. Buijsse, B.
    et al.
    Boeing, H.
    Drogan, D.
    Schulze, M. B.
    Feskens, E. J.
    Amiano, P.
    Barricarte, A.
    Clavel-Chapelon, F.
    de Lauzon-Guillain, B.
    Fagherazzi, G.
    Fonseca-Nunes, A.
    Franks, Paul
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Huerta, J. M.
    Jakobsen, M. U.
    Kaaks, R.
    Key, T. J.
    Khaw, K. T.
    Masala, G.
    Moskal, A.
    Nilsson, P. M.
    Overvad, K.
    Pala, V.
    Panico, S.
    Redondo, M. L.
    Ricceri, F.
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Sanchez, M-J
    Sluijs, I.
    Spijkerman, A. M.
    Tjonneland, A.
    Tumino, R.
    van der A, D. L.
    van der Schouw, Y. T.
    Langenberg, C.
    Sharp, S. J.
    Forouhi, N. G.
    Riboli, E.
    Wareham, N. J.
    Consumption of fatty foods and incident type 2 diabetes in populations from eight European countries2015Ingår i: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 69, nr 4, s. 455-461Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND/OBJECTIVES:

    Diets high in saturated and trans fat and low in unsaturated fat may increase type 2 diabetes (T2D) risk, but studies on foods high in fat per unit weight are sparse. We assessed whether the intake of vegetable oil, butter, margarine, nuts and seeds and cakes and cookies is related to incident T2D.

    SUBJECTS/METHODS:

    A case-cohort study was conducted, nested within eight countries of the European Prospective Investigation into Cancer (EPIC), with 12 403 incident T2D cases and a subcohort of 16 835 people, identified from a cohort of 340 234 people. Diet was assessed at baseline (1991-1999) by country-specific questionnaires. Country-specific hazard ratios (HRs) across four categories of fatty foods (nonconsumers and tertiles among consumers) were combined with random-effects meta-analysis.

    RESULTS:

    After adjustment not including body mass index (BMI), nonconsumers of butter, nuts and seeds and cakes and cookies were at higher T2D risk compared with the middle tertile of consumption. Among consumers, cakes and cookies were inversely related to T2D (HRs across increasing tertiles 1.14, 1.00 and 0.92, respectively; P-trend <0.0001). All these associations attenuated upon adjustment for BMI, except the higher risk of nonconsumers of cakes and cookies (HR 1.57). Higher consumption of margarine became positively associated after BMI adjustment (HRs across increasing consumption tertiles: 0.93, 1.00 and 1.12; P-trend 0.03). Within consumers, vegetable oil, butter and nuts and seeds were unrelated to T2D.

    CONCLUSIONS:

    Fatty foods were generally not associated with T2D, apart from weak positive association for margarine. The higher risk among nonconsumers of cakes and cookies needs further explanation.

  • 31. Cai, Lina
    et al.
    Wheeler, Eleanor
    Kerrison, Nicola D.
    Luan, Jian'an
    Deloukas, Panos
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Department of Clinical Sciences, Clinical Research Center, Skåne University Hospital, Lund University, 20502, Malmö, Sweden.
    Amiano, Pilar
    Ardanaz, Eva
    Bonet, Catalina
    Fagherazzi, Guy
    Groop, Leif C.
    Kaaks, Rudolf
    Huerta, Jose Maria
    Masala, Giovanna
    Nilsson, Peter M.
    Overvad, Kim
    Pala, Valeria
    Panico, Salvatore
    Rodriguez-Barranco, Miguel
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Sacerdote, Carlotta
    Schulze, Matthias B.
    Spijkerman, Annemieke M. W.
    Tjonneland, Anne
    Tumino, Rosario
    van der Schouw, Yvonne T.
    Sharp, Stephen J.
    Forouhi, Nita G.
    Riboli, Elio
    McCarthy, Mark I.
    Barroso, Ines
    Langenberg, Claudia
    Wareham, Nicholas J.
    Genome-wide association analysis of type 2 diabetes in the EPIC-InterAct study2020Ingår i: Scientific Data, E-ISSN 2052-4463, Vol. 7, nr 1, artikel-id 393Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Type 2 diabetes (T2D) is a global public health challenge. Whilst the advent of genome-wide association studies has identified >400 genetic variants associated with T2D, our understanding of its biological mechanisms and translational insights is still limited. The EPIC-InterAct project, centred in 8 countries in the European Prospective Investigations into Cancer and Nutrition study, is one of the largest prospective studies of T2D. Established as a nested case-cohort study to investigate the interplay between genetic and lifestyle behavioural factors on the risk of T2D, a total of 12,403 individuals were identified as incident T2D cases, and a representative sub-cohort of 16,154 individuals was selected from a larger cohort of 340,234 participants with a follow-up time of 3.99 million person-years. We describe the results from a genome-wide association analysis between more than 8.9 million SNPs and T2D risk among 22,326 individuals (9,978 cases and 12,348 non-cases) from the EPIC-InterAct study. The summary statistics to be shared provide a valuable resource to facilitate further investigations into the genetics of T2D.

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  • 32.
    Chen, Ji
    et al.
    Exeter Centre of Excellence for Diabetes Research (EXCEED), Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, United Kingdom.
    Spracklen, Cassandra N.
    Department of Genetics, University of North Carolina, Chapel Hill, United States; Department of Biostatistics and Epidemiology, University of Massachusetts, MA, Amherst, United States.
    Marenne, Gaëlle
    Inserm, Univ Brest, EFS, Brest, France.
    Varshney, Arushi
    Department of Computational Medicine and Bioinformatics, University of Michigan, MI, Ann Arbor, United States.
    Corbin, Laura J.
    MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom; Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
    Luan, Jian'an
    MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom.
    Willems, Sara M.
    MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom.
    Wu, Ying
    Department of Genetics, University of North Carolina, Chapel Hill, United States.
    Zhang, Xiaoshuai
    MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom; Department of Biostatistics, School of Public Health, Shandong University, Jinan, China.
    Horikoshi, Momoko
    Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom; Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Laboratory for Genomics of Diabetes and Metabolism, RIKEN Centre for Integrative Medical Sciences, Yokohama, Japan.
    Boutin, Thibaud S.
    Medical Research Council Human Genetics Unit, Institute for Genetics and Molecular Medicine, Edinburgh, United Kingdom.
    Mägi, Reedik
    Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.
    Waage, Johannes
    COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
    Li-Gao, Ruifang
    Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands.
    Chan, Kei Hang Katie
    Department of Epidemiology, Brown University School of Public Health, Brown University, Providence, RI, USA; Department of Biomedical Sciences, City University of Hong Kong, Hong Kong SAR, China; Department of Electrical Engineering, City University of Hong Kong, Hong Kong SAR, China.
    Yao, Jie
    The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
    Anasanti, Mila D.
    Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom.
    Chu, Audrey Y.
    Division of Preventive Medicine, Brigham and Women's Hospital, MA, Boston, United States.
    Claringbould, Annique
    Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
    Heikkinen, Jani
    Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom.
    Hong, Jaeyoung
    Department of Biostatistics, Boston University School of Public Health, MA, Boston, United States.
    Hottenga, Jouke-Jan
    Department of Biological Psychology, Faculty of Behaviour and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam, Netherlands; Amsterdam Public Health Research Institute, Amsterdam University Medical Center, Amsterdam, Netherlands.
    Huo, Shaofeng
    CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
    Kaakinen, Marika A.
    Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom; Section of Statistical Multi-omics, Department of Clinical and Experimental Research, University of Surrey, Guildford, United Kingdom.
    Louie, Tin
    Department of Biostatistics, University of Washington, Seattle, WA, USA.
    März, Winfried
    SYNLAB Academy, SYNLAB Holding Deutschland GmbH, Mannheim, Germany; Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University Graz, Graz, Austria; Vth Department of Medicine (Nephrology, Endocrinology, Medical Faculty Mannheim, Heidelberg University, Mannheim, RheumatologyBaden-Württemberg, Germany.
    Moreno-Macias, Hortensia
    Department of Economics, Metropolitan Autonomous University, Mexico City, Mexico.
    Ndungu, Anne
    Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
    Nelson, Sarah C.
    Department of Biostatistics, University of Washington, Seattle, WA, USA.
    Nolte, Ilja M.
    Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
    North, Kari E.
    CVD Genetic Epidemiology Computational Laboratory, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, United States.
    Raulerson, Chelsea K.
    Department of Genetics, University of North Carolina, Chapel Hill, United States.
    Ray, Debashree
    Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, MD, Baltimore, United States.
    Rohde, Rebecca
    CVD Genetic Epidemiology Computational Laboratory, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, United States.
    Rybin, Denis
    Department of Biostatistics, Boston University School of Public Health, MA, Boston, United States.
    Schurmann, Claudia
    Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, NY, NY, United States; HPI Digital Health Center, Digital Health and Personalized Medicine, Hasso Plattner Institute, Potsdam, Germany.
    Sim, Xueling
    Saw Swee Hock School of Public Health, National Univeristy of Singapore and National University Health System, Singapore; Center for Statistical Genetics, University of Michigan, MI, Ann Arbor, United States; Department of Biostatistics, School of Public Health, University of Michigan, MI, Ann Arbor, United States.
    Southam, Lorraine
    Institute of Translational Genomics, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
    Stewart, Isobel D.
    MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom.
    Wang, Carol A.
    School of Medicine and Public Health, College of Health, Medicine and Wellbeing, University of Newcastle, NSW, Newcastle, Australia.
    Wang, Yujie
    CVD Genetic Epidemiology Computational Laboratory, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, United States.
    Wu, Peitao
    Department of Biostatistics, Boston University School of Public Health, MA, Boston, United States.
    Zhang, Weihua
    Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom; Department of Cardiology, Ealing Hospital, London North West Healthcare NHS Trust, London, United Kingdom.
    Ahluwalia, Tarunveer S.
    COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark; Steno Diabetes Center Copenhagen, Gentofte, Denmark; Bioinformatics Centre, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
    Appel, Emil V R
    Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
    Bielak, Lawrence F.
    Department of Epidemiology, School of Public Health, University of Michigan, MI, Ann Arbor, United States.
    Brody, Jennifer A.
    Department of Medicine, Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.
    Burtt, Noël P
    Metabolism Program, Program in Medical and Population Genetics, Broad Institute, MA, Cambridge, United States.
    Cabrera, Claudia P.
    Department of Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, Barts and The London School of Medicine and Dentistry, London, United Kingdom; NIHR Barts Cardiovascular Biomedical Research Centre, Queen Mary University of London, London, United Kingdom.
    Cade, Brian E.
    Department of Medicine, Sleep and Circadian Disorders, Brigham and Women's Hospital, MA, Boston, United States; Department of Medicine, Sleep Medicine, Harvard Medical School, MA, Boston, United States.
    Chai, Jin Fang
    Saw Swee Hock School of Public Health, National Univeristy of Singapore and National University Health System, Singapore.
    Chai, Xiaoran
    Ocular Epidemiology, Singapore Eye Research Institute, Singapore National Eye Centre, Singapore; Department of Ophthalmology, National University of Singapore and National University Health System, Singapore.
    Chang, Li-Ching
    Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
    Chen, Chien-Hsiun
    Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
    Chen, Brian H.
    Department of Epidemiology, Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, United States.
    Chitrala, Kumaraswamy Naidu
    Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, MD, Baltimore, United States.
    Chiu, Yen-Feng
    Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan.
    de Haan, Hugoline G.
    Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands.
    Delgado, Graciela E.
    Vth Department of Medicine (Nephrology, Endocrinology, Medical Faculty Mannheim, Heidelberg University, Mannheim, RheumatologyBaden-Württemberg, Germany.
    Demirkan, Ayse
    Section of Statistical Multi-omics, Department of Clinical and Experimental Research, University of Surrey, Guildford, United Kingdom; Department of Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands.
    Duan, Qing
    Department of Genetics, University of North Carolina, Chapel Hill, United States; Department of Statistics, University of North Carolina at Chapel Hill, Chapel Hill, United States.
    Engmann, Jorgen
    Institute of Cardiovascular Science, University College London, London, United Kingdom.
    Fatumo, Segun A.
    Uganda Medical Informatics Centre (UMIC), MRC/UVRI and London School of Hygiene & Tropical Medicine (Uganda Research Unit), Entebbe, Uganda; London School of Hygiene & Tropical Medicine, London, United Kingdom; H3Africa Bioinformatics Network (H3ABioNet) Node, Centre for Genomics Research and Innovation, Abuja, Nigeria.
    Gayán, Javier
    Sevilla, Spain.
    Giulianini, Franco
    Division of Preventive Medicine, Brigham and Women's Hospital, MA, Boston, United States.
    Gong, Jung Ho
    Department of Epidemiology, Brown University School of Public Health, Brown University, Providence, RI, USA.
    Gustafsson, Stefan
    Molecular Epidemiology and Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Hai, Yang
    Department of Statistics, University of Auckland, Science Center, Auckland, New Zealand.
    Hartwig, Fernando P.
    MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom; Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil.
    He, Jing
    Department of Medicine, Epidemiology, Vanderbilt University Medical Center, TN, Nashville, United States.
    Heianza, Yoriko
    Department of Epidemiology, Tulane University Obesity Research Center, Tulane University, LA, New Orleans, United States.
    Huang, Tao
    Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.
    Huerta-Chagoya, Alicia
    Molecular Biology and Genomic Medicine Unit, National Council for Science and Technology, Mexico City, Mexico; Molecular Biology and Genomic Medicine Unit, National Institute of Medical Sciences and Nutrition, Mexico City, Mexico.
    Hwang, Mi Yeong
    Division of Genome Science, Department of Precision Medicine, Cheongju, National Institute of Health, South Korea.
    Jensen, Richard A.
    Department of Medicine, Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.
    Kawaguchi, Takahisa
    Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
    Kentistou, Katherine A.
    Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, United Kingdom; Centre for Cardiovascular Sciences, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
    Kim, Young Jin
    Division of Genome Science, Department of Precision Medicine, Cheongju, National Institute of Health, South Korea.
    Kleber, Marcus E.
    Vth Department of Medicine (Nephrology, Endocrinology, Medical Faculty Mannheim, Heidelberg University, Mannheim, RheumatologyBaden-Württemberg, Germany.
    Kooner, Ishminder K.
    Department of Cardiology, Ealing Hospital, London North West Healthcare NHS Trust, London, United Kingdom.
    Lai, Shuiqing
    Department of Epidemiology, Brown University School of Public Health, Brown University, Providence, RI, USA.
    Lange, Leslie A.
    Department of Medicine, Divison of Biomedical Informatics and Personalized Medicine, University of Colorado Anschutz Medical Campus, CO, Denver, United States.
    Langefeld, Carl D.
    Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, United States.
    Lauzon, Marie
    The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
    Li, Man
    Department of Medicine, Division of Nephrology and Hypertension, University of Utah, UT, Salt Lake City, United States.
    Ligthart, Symen
    Department of Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands.
    Liu, Jun
    Department of Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands; Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
    Loh, Marie
    Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
    Long, Jirong
    Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, TN, Nashville, United States.
    Lyssenko, Valeriya
    Department of Clinical Science, Center for Diabetes Research, University of Bergen, Bergen, Norway; Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Malmo, Sweden.
    Mangino, Massimo
    Department of Twin Research and Genetic Epidemiology, School of Life Course Sciences, King's College London, London, United Kingdom; NIHR Biomedical Research Centre, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
    Marzi, Carola
    Institute of Epidemiology, Research Unit of Molecular Epidemiology, Helmholtz Zentrum München Research Center for Environmental Health, Neuherberg, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany.
    Montasser, May E.
    Department of Medicine, Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, MD, Baltimore, United States.
    Nag, Abhishek
    Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
    Nakatochi, Masahiro
    Public Health Informatics Unit, Department of Integrated Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan.
    Noce, Damia
    Institute for Biomedicine, Eurac Research, Bolzano, Italy.
    Noordam, Raymond
    Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, Netherlands.
    Pistis, Giorgio
    Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche (CNR), Monserrato, Italy.
    Preuss, Michael
    Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, NY, NY, United States; Mindich Child Health and Development Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, NY, NY, United States.
    Raffield, Laura
    Department of Genetics, University of North Carolina, Chapel Hill, United States.
    Rasmussen-Torvik, Laura J.
    Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, United States.
    Rich, Stephen S.
    Center for Public Health Genomics, University of Virginia, VA, Charlottesville, United States; Department of Public Health Sciences, University of Virginia, VA, Charlottesville, United States.
    Robertson, Neil R.
    Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom; Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
    Rueedi, Rico
    Department of Computational Biology, University of Lausanne, Lausanne, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland.
    Ryan, Kathleen
    Department of Medicine, Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, MD, Baltimore, United States.
    Sanna, Serena
    Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, Netherlands; Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche (CNR), Monserrato, Italy.
    Saxena, Richa
    Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, MA, Boston, United States; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, MA, Boston, United States; Program in Medical and Population Genetics, Broad Institute, MA, Cambridge, United States.
    Schraut, Katharina E.
    Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, United Kingdom; Centre for Cardiovascular Sciences, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom.
    Sennblad, Bengt
    Department of Cell and Molecular Biology, National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Setoh, Kazuya
    Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
    Smith, Albert V.
    Department of Biostatistics, University of Michigan, MI, Ann Arbor, United States; Icelandic Heart Association, Kopavogur, Iceland.
    Sparsø, Thomas
    Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
    Strawbridge, Rona J.
    Institute of Health and Wellbeing, University of Glasgow, Glasgow, United Kingdom; Department of Medicine Solna, Cardiovascular Medicine, Karolinska Institutet, Stockholm, Sweden.
    Takeuchi, Fumihiko
    National Center for Global Health and Medicine, Tokyo, Japan.
    Tan, Jingyi
    The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
    Trompet, Stella
    Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, Netherlands; Department of Cardiology, Leiden University Medical Center, Leiden, Netherlands.
    van den Akker, Erik
    Department of Biomedical Data Sciences, Molecular Epidemiology, Leiden University Medical Center, Leiden, Netherlands; Department of Pattern Recognition and Bioinformatics, Delft University of Technology, Delft, Netherlands; Department of Biomedical Data Sciences, Leiden Computational Biology Center, Leiden University Medical Center, Leiden, Netherlands.
    van der Most, Peter J.
    Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
    Verweij, Niek
    Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands; Genomics PLC, Oxford, United Kingdom.
    Vogel, Mandy
    Center of Pediatric Research, University Children's Hospital Leipzig, University of Leipzig Medical Center, Leipzig, Germany.
    Wang, Heming
    Department of Medicine, Sleep and Circadian Disorders, Brigham and Women's Hospital, MA, Boston, United States; Department of Medicine, Sleep Medicine, Harvard Medical School, MA, Boston, United States.
    Wang, Chaolong
    Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore.
    Wang, Nan
    Department of Preventive Medicine, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA; University of Southern California Diabetes and Obesity Research Institute, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA.
    Warren, Helen R.
    Department of Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, Barts and The London School of Medicine and Dentistry, London, United Kingdom; NIHR Barts Cardiovascular Biomedical Research Centre, Queen Mary University of London, London, United Kingdom.
    Wen, Wanqing
    Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, TN, Nashville, United States.
    Wilsgaard, Tom
    Department of Community Medicine, Faculty of Health Sciences, UIT the Arctic University of Norway, Tromsø, Norway.
    Wong, Andrew
    MRC Unit for Lifelong Health and Ageing at University College London, London, United Kingdom.
    Wood, Andrew R.
    Exeter Centre of Excellence for Diabetes Research (EXCEED), Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, United Kingdom.
    Xie, Tian
    Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
    Zafarmand, Mohammad Hadi
    Department of Public Health, Amsterdam Public Health Research Institute, Amsterdam University Medical Center, Amsterdam, Netherlands; Department of Clinical Epidemiology, Biostatistics, Bioinformatics, Amsterdam Public Health Research Institute, Amsterdam University Medical Center, Amsterdam, Netherlands.
    Zhao, Jing-Hua
    Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom.
    Zhao, Wei
    Department of Epidemiology, School of Public Health, University of Michigan, MI, Ann Arbor, United States.
    Amin, Najaf
    Department of Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands; Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
    Arzumanyan, Zorayr
    The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
    Astrup, Arne
    Department of Nutrition, Exercise, Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
    Bakker, Stephan J L
    Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
    Baldassarre, Damiano
    Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy; Centro Cardiologico Monzino, IRCCS, Milan, Italy.
    Beekman, Marian
    Department of Biomedical Data Sciences, Molecular Epidemiology, Leiden University Medical Center, Leiden, Netherlands.
    Bergman, Richard N.
    Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
    Bertoni, Alain
    Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, United States.
    Blüher, Matthias
    Medical Department III-Endocrinology, Nephrology, University of Leipzig Medical Center, Rheumatology, Leipzig, Germany.
    Bonnycastle, Lori L.
    Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institues of Health, MD, Bethesda, United States.
    Bornstein, Stefan R.
    Department for Prevention and Care of Diabetes, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
    Bowden, Donald W.
    Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, United States.
    Cai, Qiuyin
    Department of Medicine, Epidemiology, Vanderbilt University Medical Center, TN, Nashville, United States.
    Campbell, Archie
    Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom; Usher Institute, University of Edinburgh, Edinburgh, United Kingdom.
    Campbell, Harry
    Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, United Kingdom.
    Chang, Yi Cheng
    Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Medical Genomics and Proteomics, National Taiwan University, Taipei, Taiwan.
    de Geus, Eco J C
    Department of Biological Psychology, Faculty of Behaviour and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam, Netherlands; Amsterdam Public Health Research Institute, Amsterdam University Medical Center, Amsterdam, Netherlands.
    Dehghan, Abbas
    Department of Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands.
    Du, Shufa
    Department of Nutrition, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, United States.
    Eiriksdottir, Gudny
    Icelandic Heart Association, Kopavogur, Iceland.
    Farmaki, Aliki Eleni
    Department of Population Science and Experimental Medicine, Institute of Cardiovascular Science, University College London, London, United Kingdom; Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University of Athens, Athens, Greece.
    Frånberg, Mattias
    Department of Medicine Solna, Cardiovascular Medicine, Karolinska Institutet, Stockholm, Sweden.
    Fuchsberger, Christian
    Institute for Biomedicine, Eurac Research, Bolzano, Italy.
    Gao, Yutang
    Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China.
    Gjesing, Anette P.
    Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
    Goel, Anuj
    Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.
    Han, Sohee
    Division of Genome Science, Department of Precision Medicine, Cheongju, National Institute of Health, South Korea.
    Hartman, Catharina A.
    Department of Psychiatry, Interdisciplinary Center Psychopathy and Emotion Regulation, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
    Herder, Christian
    Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany; Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany; German Center for Diabetes Research (DZD), Düsseldorf, Germany.
    Hicks, Andrew A.
    Institute for Biomedicine, Eurac Research, Bolzano, Italy.
    Hsieh, Chang-Hsun
    Internal Medicine, Endocrine and Metabolism, Tri-Service General Hospital, Taipei, Taiwan; School of Medicine, National Defense Medical Center, Taipei, Taiwan.
    Hsueh, Willa A.
    Internal Medicine, Endocrinology, Diabetes and Metabolism, Diabetes and Metabolism Research Center, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
    Ichihara, Sahoko
    Department of Environmental and Preventive Medicine, Jichi Medical University School of Medicine, Shimotsuke, Japan.
    Igase, Michiya
    Department of Anti-aging Medicine, Ehime University Graduate School of Medicine, Toon, Japan.
    Ikram, M Arfan
    Department of Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands.
    Johnson, W Craig
    Department of Biostatistics, University of Washington, Seattle, WA, USA.
    Jørgensen, Marit E.
    Steno Diabetes Center Copenhagen, Gentofte, Denmark; National Institute of Public Health, University of Southern Denmark, Odense, Denmark.
    Joshi, Peter K.
    Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, United Kingdom.
    Kalyani, Rita R.
    Department of Medicine, Endocrinology, Diabetes and Metabolism, Johns Hopkins University School of Medicine, MD, Baltimore, United States.
    Kandeel, Fouad R.
    Clinical Diabetes, Endocrinology and Metabolism, Translational Research and Cellular Therapeutics, Beckman Research Institute of the City of Hope, Duarte, CA, United States.
    Katsuya, Tomohiro
    Department of Clinical Gene Therapy, Osaka University Graduate School of Medicine, Suita, Japan; Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Suita, Japan.
    Khor, Chiea Chuen
    Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore.
    Kiess, Wieland
    Center of Pediatric Research, University Children's Hospital Leipzig, University of Leipzig Medical Center, Leipzig, Germany.
    Kolcic, Ivana
    Department of Public Health, University of Split School of Medicine, Split, Croatia.
    Kuulasmaa, Teemu
    Institute of Biomedicine, Bioinformatics Center, Univeristy of Eastern Finland, Kuopio, Finland.
    Kuusisto, Johanna
    Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
    Läll, Kristi
    Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.
    Lam, Kelvin
    The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
    Lawlor, Deborah A.
    MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom; Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
    Lee, Nanette R.
    USC-Office of Population Studies Foundation, University of San Carlos, Cebu City, Philippines; Department of Anthropology, Sociology and History, University of San Carlos, Cebu City, Philippines.
    Lemaitre, Rozenn N.
    Department of Medicine, Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.
    Li, Honglan
    State Key Laboratory of Oncogene and Related Genes and Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
    Lin, Shih-Yi
    Center for Geriatrics and Gerontology, Taichung Veterans General Hospital, Taichung, Taiwan; National Defense Medical Center, National Yang-Ming University, Taipei, Taiwan.
    Lindström, Jaana
    Diabetes Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland.
    Linneberg, Allan
    Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
    Liu, Jianjun
    Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore; Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore.
    Lorenzo, Carlos
    Department of Medicine, University of Texas Health Sciences Center, TX, San Antonio, United States.
    Matsubara, Tatsuaki
    Department of Internal Medicine, Aichi Gakuin University School of Dentistry, Nagoya, Japan.
    Matsuda, Fumihiko
    Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
    Mingrone, Geltrude
    Department of Diabetes, Diabetes, Nutritional Sciences, James Black Centre, King's College London, London, United Kingdom.
    Mooijaart, Simon
    Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, Netherlands.
    Moon, Sanghoon
    Division of Genome Science, Department of Precision Medicine, Cheongju, National Institute of Health, South Korea.
    Nabika, Toru
    Department of Functional Pathology, Shimane University School of Medicine, Izumo, Japan.
    Nadkarni, Girish N.
    Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, NY, NY, United States.
    Nadler, Jerry L.
    Department of Medicine and Pharmacology, New York Medical College School of Medicine, Valhalla, NY, USA.
    Nelis, Mari
    Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.
    Neville, Matt J.
    Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom; Oxford NIHR Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.
    Norris, Jill M.
    Colorado School of Public Health, University of Colorado Anschutz Medical Campus, CO, Aurora, United States.
    Ohyagi, Yasumasa
    Department of Geriatric Medicine and Neurology, Ehime University Graduate School of Medicine, Toon, Japan.
    Peters, Annette
    German Center for Diabetes Research (DZD), Neuherberg, Germany; Institute of Epidemiology, Helmholtz Zentrum München Research Center for Environmental Health, Neuherberg, Germany; Institute for Medical Information Processing, Biometry and Epidemiology, Ludwig-Maximilians University Munich, Munich, Germany.
    Peyser, Patricia A.
    Department of Epidemiology, School of Public Health, University of Michigan, MI, Ann Arbor, United States.
    Polasek, Ozren
    Department of Public Health, University of Split School of Medicine, Split, Croatia; Gen-Info, Zagreb, Croatia.
    Qi, Qibin
    Department of Epidemiology and Population Health, Albert Einstein College of Medicine, NY, NY, United States.
    Raven, Dennis
    Department of Psychiatry, Interdisciplinary Center Psychopathy and Emotion Regulation, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
    Reilly, Dermot F.
    Genetics and Pharmacogenomics, Merck Sharp & Dohme, Kenilworth, United States.
    Reiner, Alex
    Department of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
    Rivideneira, Fernando
    Department of Internal Medicine, Erasmus Medical Center, Rotterdam, Netherlands.
    Roll, Kathryn
    The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
    Rudan, Igor
    Centre for Global Health, Usher Institute, University of Edinburgh, Edinburgh, United Kingdom.
    Sabanayagam, Charumathi
    Ocular Epidemiology, Singapore Eye Research Institute, Singapore National Eye Centre, Singapore; Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore.
    Sandow, Kevin
    The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
    Sattar, Naveed
    BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.
    Schürmann, Annette
    German Center for Diabetes Research (DZD), Neuherberg, Germany; Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
    Shi, Jinxiu
    Department of Genetics, Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai (CHGC) and Shanghai Academy of Science & Technology (SAST), Shanghai, China.
    Stringham, Heather M.
    Center for Statistical Genetics, University of Michigan, MI, Ann Arbor, United States; Department of Biostatistics, School of Public Health, University of Michigan, MI, Ann Arbor, United States.
    Taylor, Kent D.
    The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
    Teslovich, Tanya M.
    Sarepta Therapeutics, MA, Cambridge, United States.
    Thuesen, Betina
    Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.
    Timmers, Paul R H J
    Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, United Kingdom; Medical Research Council Human Genetics Unit, Institute for Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom.
    Tremoli, Elena
    Centro Cardiologico Monzino, IRCCS, Milan, Italy.
    Tsai, Michael Y.
    Department of Laboratory Medicine and Pathology, University of Minnesota, MN, Minneapolis, United States.
    Uitterlinden, Andre
    Department of Internal Medicine, Erasmus Medical Center, Rotterdam, Netherlands.
    van Dam, Rob M.
    Saw Swee Hock School of Public Health, National Univeristy of Singapore and National University Health System, Singapore; Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore; Department of Nutrition, Harvard T. H. Chan School of Public Health, MA, Boston, United States.
    van Heemst, Diana
    Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, Netherlands.
    van Hylckama Vlieg, Astrid
    Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands.
    van Vliet-Ostaptchouk, Jana V.
    Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
    Vangipurapu, Jagadish
    Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland.
    Vestergaard, Henrik
    Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Medicine, Bornholms Hospital, Denmark.
    Wang, Tao
    Department of Epidemiology and Population Health, Albert Einstein College of Medicine, NY, NY, United States.
    Willems van Dijk, Ko
    Department of Internal Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, Netherlands; Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, Netherlands; Department of Human Genetics, Leiden University Medical Center, Leiden, Netherlands.
    Zemunik, Tatijana
    Department of Human Biology, University of Split School of Medicine, Split, Croatia.
    Abecasis, Gonçalo R
    Department of Biostatistics, School of Public Health, University of Michigan, MI, Ann Arbor, United States.
    Adair, Linda S.
    Department of Nutrition, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, United States; Carolina Population Center, University of North Carolina, Chapel Hill, United States.
    Aguilar-Salinas, Carlos Alberto
    Department of Endocrinology and Metabolism, Instituto Nacional de Ciencias Medicas y Nutricion, Mexico City, Mexico; Unidad de Investigación de Enfermedades Metabólicas, Instituto Nacional de Ciencias Médicas y Nutrición and Tec Salud, Mexico City, Mexico; Instituto Tecnológico y de Estudios Superiores de Monterrey Tec Salud, Monterrey, Mexico.
    Alarcón-Riquelme, Marta E.
    Department of Medical Genomics, Pfizer/University of Granada/Andalusian Government Center for Genomics and Oncological Research (GENYO), Granada, Spain; Institute for Environmental Medicine, Chronic Inflammatory Diseases, Karolinska Institutet, Solna, Sweden.
    An, Ping
    Department of Genetics, Division of Statistical Genomics, Washington University School of Medicine, St Louis, MO, USA.
    Aviles-Santa, Larissa
    Clinical and Health Services Research, National Institute on Minority Health and Health Disparities, MD, Bethesda, United States.
    Becker, Diane M.
    Department of Medicine, General Internal Medicine, Johns Hopkins University School of Medicine, MD, Baltimore, United States.
    Beilin, Lawrence J.
    Medical School, Royal Perth Hospital Unit, University of Western Australia, WA, Perth, Australia.
    Bergmann, Sven
    Department of Computational Biology, University of Lausanne, Lausanne, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland; Department of Integrative Biomedical Sciences, University of Cape Town, Cape Town, South Africa.
    Bisgaard, Hans
    COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
    Black, Corri
    Aberdeen Centre for Health Data Science, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United Kingdom.
    Boehnke, Michael
    Center for Statistical Genetics, University of Michigan, MI, Ann Arbor, United States; Department of Biostatistics, School of Public Health, University of Michigan, MI, Ann Arbor, United States.
    Boerwinkle, Eric
    Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, TX, Houston, United States; Human Genome Sequencing Center, Baylor College of Medicine, TX, Houston, United States.
    Böhm, Bernhard O.
    Division of Endocrinology and Diabetes, Graduate School of Molecular Endocrinology and Diabetes, University of Ulm, Ulm, Germany; LKC School of Medicine, Nanyang Technological University, Singapore and Imperial College London, Singapore.
    Bønnelykke, Klaus
    COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
    Boomsma, D.I.
    Department of Biological Psychology, Faculty of Behaviour and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam, Netherlands; Amsterdam Public Health Research Institute, Amsterdam University Medical Center, Amsterdam, Netherlands.
    Bottinger, Erwin P.
    Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, NY, NY, United States; Hasso Plattner Institute for Digital Health at Mount Sinai, Icahn School of Medicine at Mount Sinai, NY, NY, United States; Digital Health Center, Hasso Plattner Institut, University Potsdam, Potsdam, Germany.
    Buchanan, Thomas A.
    University of Southern California Diabetes and Obesity Research Institute, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA; Department of Medicine, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA; Department of Physiology and Neuroscience, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA.
    Canouil, Mickaël
    European Institute for Diabetes (EGID), Université de Lille, Lille, France; European Institute for Diabetes (EGID), Institut Pasteur de Lille, Lille, France.
    Caulfield, Mark J.
    Department of Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, Barts and The London School of Medicine and Dentistry, London, United Kingdom; NIHR Barts Cardiovascular Biomedical Research Centre, Queen Mary University of London, London, United Kingdom.
    Chambers, John C.
    Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom; Department of Cardiology, Ealing Hospital, London North West Healthcare NHS Trust, London, United Kingdom; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore; Imperial College Healthcare NHS Trust, Imperial College London, London, United Kingdom; MRC-PHE Centre for Environment and Health, Imperial College London, London, United Kingdom.
    Chasman, Daniel I.
    Division of Preventive Medicine, Brigham and Women's Hospital, MA, Boston, United States; Harvard Medical School, MA, Boston, United States.
    Chen, Yii-Der Ida
    The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
    Cheng, Ching-Yu
    Ocular Epidemiology, Singapore Eye Research Institute, Singapore National Eye Centre, Singapore; Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore.
    Collins, Francis S.
    Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institues of Health, MD, Bethesda, United States.
    Correa, Adolfo
    Department of Medicine, Jackson Heart Study, University of Mississippi Medical Center, MS, Jackson, United States.
    Cucca, Francesco
    Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche (CNR), Monserrato, Italy.
    de Silva, H Janaka
    Department of Medicine, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka.
    Dedoussis, George
    Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University of Athens, Kallithea, Greece.
    Elmståhl, Sölve
    Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Evans, Michele K.
    Laboratory of Epidemiology and Population Sciences, National Institute on Aging Intramural Research Program, National Institutes of Health, MD, Baltimore, United States.
    Ferrannini, Ele
    CNR Institute of Clinical Physiology, Pisa, Italy.
    Ferrucci, Luigi
    Intramural Research Program, National Institute of Aging, MD, Baltimore, United States.
    Florez, Jose C.
    Program in Medical and Population Genetics, Broad Institute, MA, Cambridge, United States; Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, MA, Boston, United States; Department of Medicine, Harvard Medical School, MA, Boston, United States.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa. Department of Clinical Sciences, Lund University Diabetes Centre, Lund University, Malmo, Sweden.
    Frayling, Timothy M.
    Exeter Centre of Excellence for Diabetes Research (EXCEED), Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, United Kingdom.
    Froguel, Philippe
    European Institute for Diabetes (EGID), Université de Lille, Lille, France; European Institute for Diabetes (EGID), Institut Pasteur de Lille, Lille, France; Department of Genomics of Common Disease, Imperial College London, London, United Kingdom.
    Gigante, Bruna
    Department of Medicine, Cardiovascular Medicine, Karolinska Institutet, Stockholm, Sweden.
    Goodarzi, Mark O.
    Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
    Gordon-Larsen, Penny
    Department of Nutrition, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, United States; Carolina Population Center, University of North Carolina, Chapel Hill, United States.
    Grallert, Harald
    Institute of Epidemiology, Research Unit of Molecular Epidemiology, Helmholtz Zentrum München Research Center for Environmental Health, Neuherberg, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany.
    Grarup, Niels
    Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
    Grimsgaard, Sameline
    Department of Community Medicine, Faculty of Health Sciences, UIT the Arctic University of Norway, Tromsø, Norway.
    Groop, Leif
    Diabetes Centre, Lund University, Lund, Sweden; Finnish Institute of Molecular Medicine, Helsinki University, Helsinki, Finland.
    Gudnason, Vilmundur
    Icelandic Heart Association, Kopavogur, Iceland; Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland.
    Guo, Xiuqing
    The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
    Hamsten, Anders
    Department of Medicine Solna, Cardiovascular Medicine, Karolinska Institutet, Stockholm, Sweden.
    Hansen, Torben
    Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
    Hayward, Caroline
    Medical Research Council Human Genetics Unit, Institute for Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom.
    Heckbert, Susan R.
    Department of Epidemiology, Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.
    Horta, Bernardo L.
    Postgraduate Program in Epidemiology, Federal University of Pelotas, Pelotas, Brazil.
    Huang, Wei
    Department of Genetics, Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai (CHGC) and Shanghai Academy of Science & Technology (SAST), Shanghai, China.
    Ingelsson, Erik
    Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
    James, Pankow S.
    Division of Epidemiology and Community Health, University of Minnesota, MN, Minneapolis, United States.
    Jarvelin, Marjo-Ritta
    Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, United Kingdom; Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland; Unit of Primary Health Care, Oulu Univerisity Hospital, OYS, Oulu, Finland; Department of Life Sciences, College of Health and Life Sciences, Brunel University London, London, United Kingdom.
    Jonas, Jost B.
    Department of Ophthalmology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Beijing Institute of Ophthalmology, Beijing Ophthalmology and Visual Science Key Lab, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China; Institute of Molecular and Clinical Ophthalmology Basel IOB, Basel, Switzerland.
    Jukema, J Wouter
    Department of Cardiology, Leiden University Medical Center, Leiden, Netherlands; Netherlands Heart Institute, Utrecht, Netherlands.
    Kaleebu, Pontiano
    Entebbe, Uganda.
    Kaplan, Robert
    Department of Epidemiology and Population Health, Albert Einstein College of Medicine, NY, NY, United States; Department of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
    Kardia, Sharon L R
    Department of Epidemiology, School of Public Health, University of Michigan, MI, Ann Arbor, United States.
    Kato, Norihiro
    National Center for Global Health and Medicine, Tokyo, Japan.
    Keinanen-Kiukaanniemi, Sirkka M.
    Faculty of Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland; Unit of General Practice, Oulu University Hospital, Oulu, Finland.
    Kim, Bong-Jo
    Division of Genome Science, Department of Precision Medicine, Cheongju, National Institute of Health, South Korea.
    Kivimaki, Mika
    Department of Epidemiology and Public Health, University College London, London, United Kingdom.
    Koistinen, Heikki A.
    Department of Public Health Solutions, Finnish Institute for Health and Welfare, Helsinki, Finland; Department of Medicine, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; Minerva Foundation Institute for Medical Research, Helsinki, Finland.
    Kooner, Jaspal S.
    Department of Cardiology, Ealing Hospital, London North West Healthcare NHS Trust, London, United Kingdom; Imperial College Healthcare NHS Trust, Imperial College London, London, United Kingdom; MRC-PHE Centre for Environment and Health, Imperial College London, London, United Kingdom; National Heart and Lung Institute, Imperial College London, London, United Kingdom.
    Körner, Antje
    Center of Pediatric Research, University Children's Hospital Leipzig, University of Leipzig Medical Center, Leipzig, Germany.
    Kovacs, Peter
    Medical Department III-Endocrinology, Nephrology, University of Leipzig Medical Center, Rheumatology, Leipzig, Germany; IFB Adiposity Diseases, University of Leipzig Medical Center, Leipzig, Germany.
    Kuh, Diana
    MRC Unit for Lifelong Health and Ageing at University College London, London, United Kingdom.
    Kumari, Meena
    Institute for Social and Economic Research, University of Essex, Colchester, United Kingdom.
    Kutalik, Zoltan
    Swiss Institute of Bioinformatics, Lausanne, Switzerland; University Institute of Primary Care and Public Health, Division of Biostatistics, University of Lausanne, Lausanne, Switzerland.
    Laakso, Markku
    Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
    Lakka, Timo A.
    Institute of Biomedicine, School of Medicine, University of Eastern Finland, Kuopio, Finland; Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland; Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, Finland.
    Launer, Lenore J.
    Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, MD, Baltimore, United States.
    Leander, Karin
    Institute of Environmental Medicine, Cardiovascular and Nutritional Epidemiology, Karolinska Institutet, Stockholm, Sweden.
    Li, Huaixing
    CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
    Lin, Xu
    CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
    Lind, Lars
    Department of Medical Sciences, University of Uppsala, Uppsala, Sweden.
    Lindgren, Cecilia
    Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Big Data Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom; Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, United Kingdom.
    Liu, Simin
    Department of Epidemiology, Brown University School of Public Health, Brown University, Providence, RI, USA.
    Loos, Ruth J F
    Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, NY, NY, United States; Mindich Child Health and Development Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, NY, NY, United States.
    Magnusson, Patrik K E
    Department of Medical Epidemiology and Biostatistics and the Swedish Twin Registry, Karolinska Institutet, Stockholm, Sweden.
    Mahajan, Anubha
    Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Genentech, South San Francisco, CA, USA.
    Metspalu, Andres
    Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.
    Mook-Kanamori, Dennis O.
    Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands; Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, Netherlands.
    Mori, Trevor A.
    Medical School, Royal Perth Hospital Unit, University of Western Australia, WA, Perth, Australia.
    Munroe, Patricia B.
    Department of Clinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, Barts and The London School of Medicine and Dentistry, London, United Kingdom; NIHR Barts Cardiovascular Biomedical Research Centre, Queen Mary University of London, London, United Kingdom.
    Njølstad, Inger
    Department of Community Medicine, Faculty of Health Sciences, UIT the Arctic University of Norway, Tromsø, Norway.
    O'Connell, Jeffrey R.
    Department of Medicine, Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, MD, Baltimore, United States.
    Oldehinkel, Albertine J.
    Department of Psychiatry, Interdisciplinary Center Psychopathy and Emotion Regulation, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
    Ong, Ken K.
    MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom.
    Padmanabhan, Sandosh
    Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.
    Palmer, Colin N A
    Division of Population Health and Genomics, School of Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, United Kingdom.
    Palmer, Nicholette D.
    Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, United States.
    Pedersen, Oluf
    Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
    Pennell, Craig E.
    School of Medicine and Public Health, College of Health, Medicine and Wellbeing, University of Newcastle, NSW, Newcastle, Australia.
    Porteous, David J.
    Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom.
    Pramstaller, Peter P.
    Institute for Biomedicine, Eurac Research, Bolzano, Italy.
    Province, Michael A.
    Department of Genetics, Division of Statistical Genomics, Washington University School of Medicine, St Louis, MO, USA.
    Psaty, Bruce M.
    Department of Medicine, Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA; Department of Epidemiology, Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA; Department of Health Services, Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.
    Qi, Lu
    Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, LA, New Orleans, United States.
    Raffel, Leslie J.
    Department of Pediatrics, Genetic and Genomic Medicine, University of California, Irvine, Irvine, CA, USA.
    Rauramaa, Rainer
    Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, Finland.
    Redline, Susan
    Department of Medicine, Sleep and Circadian Disorders, Brigham and Women's Hospital, MA, Boston, United States; Department of Medicine, Sleep Medicine, Harvard Medical School, MA, Boston, United States.
    Ridker, Paul M.
    Division of Preventive Medicine, Brigham and Women's Hospital, MA, Boston, United States; Havard Medical School, MA, Boston, United States.
    Rosendaal, Frits R.
    Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands.
    Saaristo, Timo E.
    Finnish Diabetes Association, Tampere, Finland; , Pirkanmaa Hospital District, Tampere, Finland.
    Sandhu, Manjinder
    Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
    Saramies, Jouko
    South Karelia Central Hospital, Lappeenranta, Finland.
    Schneiderman, Neil
    Department of Psychology, University of Miami, FL, Miami, United States.
    Schwarz, Peter
    German Center for Diabetes Research (DZD), Neuherberg, Germany; Department for Prevention and Care of Diabetes, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; Paul Langerhans Institute Dresden of the Helmholtz Center Munich, University Hospital and Faculty of Medicine, Dresden, Germany.
    Scott, Laura J.
    Center for Statistical Genetics, University of Michigan, MI, Ann Arbor, United States; Department of Biostatistics, School of Public Health, University of Michigan, MI, Ann Arbor, United States.
    Selvin, Elizabeth
    Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, MD, Baltimore, United States.
    Sever, Peter
    National Heart and Lung Institute, Imperial College London, London, United Kingdom.
    Shu, Xiao-Ou
    Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, TN, Nashville, United States.
    Slagboom, P Eline
    Department of Biomedical Data Sciences, Molecular Epidemiology, Leiden University Medical Center, Leiden, Netherlands.
    Small, Kerrin S.
    Department of Twin Research and Genetic Epidemiology, School of Life Course Sciences, King's College London, London, United Kingdom.
    Smith, Blair H.
    Division of Population Health and Genomics, Ninewells Hospital and Medical School, University of Dundee, Dundee, United Kingdom.
    Snieder, Harold
    Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
    Sofer, Tamar
    Department of Medicine, Harvard Medical School, MA, Boston, United States; Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, MA, Boston, United States.
    Sørensen, Thorkild I A
    MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom; Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Public Health, Section of Epidemiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
    Spector, Tim D.
    Department of Twin Research and Genetic Epidemiology, School of Life Course Sciences, King's College London, London, United Kingdom.
    Stanton, Alice
    Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland.
    Steves, Claire J.
    Department of Twin Research and Genetic Epidemiology, School of Life Course Sciences, King's College London, London, United Kingdom; Department of Ageing and Health, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
    Stumvoll, Michael
    Medical Department III-Endocrinology, Nephrology, University of Leipzig Medical Center, Rheumatology, Leipzig, Germany.
    Sun, Liang
    CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
    Tabara, Yasuharu
    Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
    Tai, E Shyong
    Saw Swee Hock School of Public Health, National Univeristy of Singapore and National University Health System, Singapore; Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore; Cardiovascular and Metabolic Disease Signature Research Program, Duke-NUS Medical School, Singapore.
    Timpson, Nicholas J.
    MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom; Department of Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
    Tönjes, Anke
    Medical Department III-Endocrinology, Nephrology, University of Leipzig Medical Center, Rheumatology, Leipzig, Germany.
    Tuomilehto, Jaakko
    Department of Public Health Solutions, National Institute for Health and Welfare, Helsinki, Finland; Department of Public Health, University of Helsinki, Helsinki, Finland; Saudi Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia.
    Tusie, Teresa
    Molecular Biology and Genomic Medicine Unit, National Institute of Medical Sciences and Nutrition, Mexico City, Mexico; Department of Genomic Medicine and Environmental Toxicology, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico.
    Uusitupa, Matti
    Department of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
    van der Harst, Pim
    Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, Netherlands; Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
    van Duijn, Cornelia
    Department of Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands; Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
    Vitart, Veronique
    Medical Research Council Human Genetics Unit, Institute for Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom.
    Vollenweider, Peter
    Department of Medicine, Internal Medicine, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
    Vrijkotte, Tanja G M
    Department of Public Health, Amsterdam Public Health Research Institute, Amsterdam University Medical Center, Amsterdam, Netherlands.
    Wagenknecht, Lynne E.
    Department of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, United States.
    Walker, Mark
    Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.
    Wang, Ya X.
    Beijing Institute of Ophthalmology, Beijing Ophthalmology and Visual Science Key Lab, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
    Wareham, Nick J.
    MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom.
    Watanabe, Richard M.
    Department of Preventive Medicine, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA; University of Southern California Diabetes and Obesity Research Institute, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA; Department of Physiology and Neuroscience, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA.
    Watkins, Hugh
    Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.
    Wei, Wen B.
    Beijing Tongren Eye Center, Beijing Key Laboratory of Intraocular Tumor Diagnosis and Treatment, Beijing Ophthalmology & Visual Sciences Key Lab, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
    Wickremasinghe, Ananda R.
    Department of Public Health, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka.
    Willemsen, Gonneke
    Department of Biological Psychology, Faculty of Behaviour and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam, Netherlands; Amsterdam Public Health Research Institute, Amsterdam University Medical Center, Amsterdam, Netherlands.
    Wilson, James F.
    Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, United Kingdom; Medical Research Council Human Genetics Unit, Institute for Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom.
    Wong, Tien-Yin
    Ocular Epidemiology, Singapore Eye Research Institute, Singapore National Eye Centre, Singapore; Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore.
    Wu, Jer-Yuarn
    Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
    Xiang, Anny H.
    Department of Research and Evaluation, Kaiser Permanente of Southern California, Pasadena, CA, USA.
    Yanek, Lisa R.
    Department of Medicine, General Internal Medicine, Johns Hopkins University School of Medicine, MD, Baltimore, United States.
    Yengo, Loïc
    Institute for Molecular Bioscience, University of Queensland, St Lucia, QLD, Australia.
    Yokota, Mitsuhiro
    Kurume University School of Medicine, Kurume, Japan.
    Zeggini, Eleftheria
    Institute of Translational Genomics, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany; TUM School of Medicine, Technical University of Munich and Klinikum Rechts der Isar, Munich, Germany.
    Zheng, Wei
    Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, TN, Nashville, United States.
    Zonderman, Alan B.
    Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, MD, Baltimore, United States.
    Rotter, Jerome I.
    The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
    Gloyn, Anna L.
    Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom; Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Oxford NIHR Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom; Department of Pediatrics, Division of Endocrinology, Stanford School of Medicine, Stanford, CA, USA.
    McCarthy, Mark I.
    Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom; Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Oxford NIHR Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom; Genentech, South San Francisco, CA, USA; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
    Dupuis, Josée
    Department of Biostatistics, Boston University School of Public Health, MA, Boston, United States.
    Meigs, James B.
    Program in Medical and Population Genetics, Broad Institute, MA, Cambridge, United States; Department of Medicine, Harvard Medical School, MA, Boston, United States; Department of Medicine, Division of General Internal Medicine, Massachusetts General Hospital, MA, Boston, United States.
    Scott, Robert A.
    MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom.
    Prokopenko, Inga
    Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom; Section of Statistical Multi-omics, Department of Clinical and Experimental Research, University of Surrey, Guildford, United Kingdom.
    Leong, Aaron
    Harvard Medical School, MA, Boston, United States; Department of Medicine, General Internal Medicine, Massachusetts General Hospital, MA, Boston, United States; Department of Medicine, Diabetes Unit and Endocrine Unit, Massachusetts General Hospital, MA, Boston, United States.
    Liu, Ching-Ti
    Department of Biostatistics, Boston University School of Public Health, MA, Boston, United States.
    Parker, Stephen C J
    Department of Computational Medicine and Bioinformatics, University of Michigan, MI, Ann Arbor, United States; Department of Human Genetics, University of Michigan, MI, Ann Arbor, United States.
    Mohlke, Karen L.
    Department of Genetics, University of North Carolina, Chapel Hill, United States.
    Langenberg, Claudia
    MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom.
    Wheeler, Eleanor
    MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom.
    Morris, Andrew P.
    Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom; Centre for Genetics and Genomics Versus Arthritis, Division of Musculoskeletal and Dermatological Sciences, University of Manchester, Manchester, United Kingdom; Centre for Musculoskeletal Research, Division of Musculoskeletal and Dermatological Sciences, University of Manchester, Manchester, United Kingdom; Department of Biostatistics, University of Liverpool, Liverpool, United Kingdom.
    Barroso, Inês
    Exeter Centre of Excellence for Diabetes Research (EXCEED), Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, United Kingdom; MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom.
    The trans-ancestral genomic architecture of glycemic traits2021Ingår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 53, nr 6, s. 840-860Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10-8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.

  • 33. Chen, Yan
    et al.
    Estampador, Angela C
    Keller, Maria
    Poveda, Alaitz
    Dalla-Riva, Jonathan
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Renström, Frida
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Lund University, Skåne University Hospital Malmö, Malmö, Sweden.
    Kurbasic, Azra
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Lund University, Skåne University Hospital Malmö, Malmö, Sweden; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston MA, USA.
    Varga, Tibor V
    The combined effects of FADS gene variation and dietary fats in obesity-related traits in a population from the far north of Sweden: the GLACIER Study2019Ingår i: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 43, nr 4, s. 808-820Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Recent analyses in Greenlandic Inuit identified six genetic polymorphisms (rs74771917, rs3168072, rs12577276, rs7115739, rs174602 and rs174570) in the fatty acid desaturase gene cluster (FADS1-FADS2-FADS3) that are associated with multiple metabolic and anthropometric traits. Our objectives were to systematically assess whether dietary polyunsaturated fatty acid (PUFA) intake modifies the associations between genetic variants in the FADS gene cluster and cardiometabolic traits, and to functionally annotate top-ranking candidates to estimate their regulatory potential.

    METHODS: Data analyses consisted of the following: interaction analyses between the 6 candidate genetic variants and dietary PUFA intake; gene-centric joint analyses to detect interaction signals in the FADS region; haplotype-centric joint tests across 30 haplotype blocks in the FADS region to refine interaction signals; and functional annotation of top-ranking loci from the previous steps. These analyses were undertaken in Swedish adults from the GLACIER Study (N = 5,160); data on genetic variation and eight cardiometabolic traits were used.

    RESULTS: Interactions were observed between rs174570 and n-6 PUFA intake on fasting glucose (Pint = 0.005) and between rs174602 and n-3 PUFA intake on total cholesterol (Pint = 0.001). Gene-centric analyses demonstrated a statistically significant interaction effect for FADS and n-3 PUFA on triglycerides (Pint = 0.005) considering genetic main effects as random. Haplotype analyses revealed three blocks (Pint < 0.011) that could drive the interaction between FADS and n-3 PUFA on triglycerides; functional annotation of these regions showed that each block harbours a number of highly functional regulatory variants; FADS2 rs5792235 demonstrated the highest functionality score.

    CONCLUSIONS: The association between FADS variants and triglycerides may be modified by PUFA intake. The intronic FADS2 rs5792235 variant is a potential causal variant in the region, having the highest regulatory potential. However, our results suggest that multiple haplotypes may harbour functional variants in a region, rather than a single causal variant.

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  • 34. Chikowore, Tinashe
    et al.
    Chong, Michael
    Micklesfield, Lisa K.
    Ramsay, Michele
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin. Department of Clinical Sciences, Skåne University Hospital, Malmö,Sweden; Department of Nutrition, Harvard T. H.Chan School of Public Health, Boston, MA, USA.
    Pare, Guillaume
    Morris, Andrew P.
    GWAS transethnic meta-analysis of BMI in similar to 700k individuals reveals novel gene-smoking interaction in African populations2020Ingår i: Genetic Epidemiology, ISSN 0741-0395, E-ISSN 1098-2272, Vol. 44, nr 5, s. 475-476Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Sixty two percent of the 1.12 billion obese people globally reside in low‐middle income countries, 77% of which are in Africa. There is paucity of data on gene‐lifestyle interactions associated with the increasing prevalence of obesity among Africans. We hypothesised that gene‐environment interacting (GEI) variants exhibit heterogenous effects on obesity in transethnic meta‐analysis of marginal SNP associations as a result of modification by an unknown exposure that varies across populations.

    Body mass index (BMI) genome‐wide association study (GWAS) summary statistics for 678,671 individuals representative of the major global ancestries were aggregated at 21,338,816 SNPs via fixed‐effects meta‐analysis. Lead SNPs attaining genome‐wide significance ( < 5 × 10−8) were tested for heterogeneity in effects between GWAS. Lead SNPs with significant evidence of heterogeneity after Bonferroni correction were then selected for interaction analysis with selected lifestyle factors in an independent AWI‐Gen study of 10,500 African participants. Significant interaction findings were then replicated in 3,177 individuals of African ancestry in the UK Biobank.

    Of 881 lead SNPs, five had significant heterogenous effects on BMI ( < 5.7 × 10−5). Rs471094, at the CDKAL1 locus had significant interaction with smoking status, which reduced the effect of the BMI raising allele in current smokers (Betaint = −0.949 kg/m2; int = .002) compared with non‐smokers in AWI‐Gen. This finding was validated in the UK Biobank (Betaint = −1.471 kg/m2, int = .020; meta‐analysis Betaint = −1.050 kg/m2, int = .0002). Our results highlight the first gene‐lifestyle interaction on BMI in Africans and demonstrate the utility of transethnic meta‐analysis of GWAS for identifying GEI effects.

  • 35. Cooper, A. J.
    et al.
    Forouhi, N. G.
    Ye, Z.
    Buijsse, B.
    Arriola, L.
    Balkau, B.
    Barricarte, A.
    Beulens, J. W. J.
    Boeing, H.
    Buchner, F. L.
    Dahm, C. C.
    de Lauzon-Guillain, B.
    Fagherazzi, G.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Gonzalez, C.
    Grioni, S.
    Kaaks, R.
    Key, T. J.
    Masala, G.
    Navarro, C.
    Nilsson, P.
    Overvad, K.
    Panico, S.
    Ramon Quiros, J.
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Roswall, N.
    Sacerdote, C.
    Sanchez, M-J
    Slimani, N.
    Sluijs, I.
    Spijkerman, A. M. W.
    Teucher, B.
    Tjonneland, A.
    Tumino, R.
    Sharp, S. J.
    Langenberg, C.
    Feskens, E. J. M.
    Riboli, E.
    Wareham, N. J.
    Fruit and vegetable intake and type 2 diabetes: EPIC-InterAct prospective study and meta-analysis2012Ingår i: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 66, nr 10, s. 1082-1092Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Fruit and vegetable intake (FVI) may reduce the risk of type 2 diabetes (T2D), but the epidemiological evidence is inconclusive. The aim of this study is to examine the prospective association of FVI with T2D and conduct an updated meta-analysis. In the European Prospective Investigation into Cancer-InterAct (EPIC-InterAct) prospective case-cohort study nested within eight European countries, a representative sample of 16 154 participants and 12 403 incident cases of T2D were identified from 340 234 individuals with 3.99 million person-years of follow-up. For the meta-analysis we identified prospective studies on FVI and T2D risk by systematic searches of MEDLINE and EMBASE until April 2011. In EPIC-InterAct, estimated FVI by dietary questionnaires varied more than twofold between countries. In adjusted analyses the hazard ratio (95% confidence interval) comparing the highest with lowest quartile of reported intake was 0.90 (0.80-1.01) for FVI; 0.89 (0.76-1.04) for fruit and 0.94 (0.84-1.05) for vegetables. Among FV subtypes, only root vegetables were inversely associated with diabetes 0.87 (0.77-0.99). In meta-analysis using pooled data from five studies including EPIC-InterAct, comparing the highest with lowest category for FVI was associated with a lower relative risk of diabetes (0.93 (0.87-1.00)). Fruit or vegetables separately were not associated with diabetes. Among FV subtypes, only green leafy vegetable (GLV) intake (relative risk: 0.84 (0.74-0.94)) was inversely associated with diabetes. Subtypes of vegetables, such as root vegetables or GLVs may be beneficial for the prevention of diabetes, while total FVI may exert a weaker overall effect.

  • 36. Corbin, Laura J.
    et al.
    Tan, Vanessa Y.
    Hughes, David A.
    Wade, Kaitlin H.
    Paul, Dirk S.
    Tansey, Katherine E.
    Butcher, Frances
    Dudbridge, Frank
    Howson, Joanna M.
    Jallow, Momodou W.
    John, Catherine
    Kingston, Nathalie
    Lindgren, Cecilia M.
    O'Donavan, Michael
    O'Rahilly, Stephen
    Owen, Michael J.
    Palmer, Colin N. A.
    Pearson, Ewan R.
    Scott, Robert A.
    van Heel, David A.
    Whittaker, John
    Frayling, Tim
    Tobin, Martin D.
    Wain, Louise V.
    Smith, George Davey
    Evans, David M.
    Karpe, Fredrik
    McCarthy, Mark I.
    Danesh, John
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 7LE, UK; Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Clinical Research Centre, Lund University, Skåne University Hospital, Malmö, SE-205 02, Sweden; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
    Timpson, Nicholas J.
    Formalising recall by genotype as an efficient approach to detailed phenotyping and causal inference2018Ingår i: Nature Communications, E-ISSN 2041-1723, Vol. 9, artikel-id 711Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Detailed phenotyping is required to deepen our understanding of the biological mechanisms behind genetic associations. In addition, the impact of potentially modifiable risk factors on disease requires analytical frameworks that allow causal inference. Here, we discuss the characteristics of Recall-by-Genotype (RbG) as a study design aimed at addressing both these needs. We describe two broad scenarios for the application of RbG: studies using single variants and those using multiple variants. We consider the efficacy and practicality of the RbG approach, provide a catalogue of UK-based resources for such studies and present an online RbG study planner.

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  • 37. Cornelis, M C
    et al.
    Byrne, E M
    Esko, T
    Nalls, M A
    Ganna, A
    Paynter, N
    Monda, K L
    Amin, N
    Fischer, K
    Renstrom, F
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Ngwa, J S
    Huikari, V
    Cavadino, A
    Nolte, I M
    Teumer, A
    Yu, K
    Marques-Vidal, P
    Rawal, R
    Manichaikul, A
    Wojczynski, M K
    Vink, J M
    Zhao, J H
    Burlutsky, G
    Lahti, J
    Mikkilä, V
    Lemaitre, R N
    Eriksson, J
    Musani, S K
    Tanaka, T
    Geller, F
    Luan, J
    Hui, J
    Mägi, R
    Dimitriou, M
    Garcia, M E
    Ho, W-K
    Wright, M J
    Rose, L M
    Magnusson, P K E
    Pedersen, N L
    Couper, D
    Oostra, B A
    Hofman, A
    Ikram, M A
    Tiemeier, H W
    Uitterlinden, A G
    van Rooij, F J A
    Barroso, I
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Xue, L
    Kaakinen, M
    Milani, L
    Power, C
    Snieder, H
    Stolk, R P
    Baumeister, S E
    Biffar, R
    Gu, F
    Bastardot, F
    Kutalik, Z
    Jacobs, D R
    Forouhi, N G
    Mihailov, E
    Lind, L
    Lindgren, C
    Michaëlsson, K
    Morris, A
    Jensen, M
    Khaw, K-T
    Luben, R N
    Wang, J J
    Männistö, S
    Perälä, M-M
    Kähönen, M
    Lehtimäki, T
    Viikari, J
    Mozaffarian, D
    Mukamal, K
    Psaty, B M
    Döring, A
    Heath, A C
    Montgomery, G W
    Dahmen, N
    Carithers, T
    Tucker, K L
    Ferrucci, L
    Boyd, H A
    Melbye, M
    Treur, J L
    Mellström, D
    Hottenga, J J
    Prokopenko, I
    Tönjes, A
    Deloukas, P
    Kanoni, S
    Lorentzon, M
    Houston, D K
    Liu, Y
    Danesh, J
    Rasheed, A
    Mason, M A
    Zonderman, A B
    Franke, L
    Kristal, B S
    Karjalainen, J
    Reed, D R
    Westra, H-J
    Evans, M K
    Saleheen, D
    Harris, T B
    Dedoussis, G
    Curhan, G
    Stumvoll, M
    Beilby, J
    Pasquale, L R
    Feenstra, B
    Bandinelli, S
    Ordovas, J M
    Chan, A T
    Peters, U
    Ohlsson, C
    Gieger, C
    Martin, N G
    Waldenberger, M
    Siscovick, D S
    Raitakari, O
    Eriksson, J G
    Mitchell, P
    Hunter, D J
    Kraft, P
    Rimm, E B
    Boomsma, D I
    Borecki, I B
    Loos, R J F
    Wareham, N J
    Vollenweider, P
    Caporaso, N
    Grabe, H J
    Neuhouser, M L
    Wolffenbuttel, B H R
    Hu, F B
    Hyppönen, E
    Järvelin, M-R
    Cupples, L A
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Nutrition, Harvard School of Public Health, Boston, MA, USA; Lund Univ, Dept Clin Sci, Malmo, Sweden.
    Ridker, P M
    van Duijn, C M
    Heiss, G
    Metspalu, A
    North, K E
    Ingelsson, E
    Nettleton, J A
    van Dam, R M
    Chasman, D I
    Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption2015Ingår i: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 20, nr 5, s. 647-656Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to 91 462 coffee consumers of European ancestry with top single-nucleotide polymorphisms (SNPs) followed-up in ~30 062 and 7964 coffee consumers of European and African-American ancestry, respectively. Studies from both stages were combined in a trans-ethnic meta-analysis. Confirmed loci were examined for putative functional and biological relevance. Eight loci, including six novel loci, met GW significance (log10Bayes factor (BF)>5.64) with per-allele effect sizes of 0.03-0.14 cups per day. Six are located in or near genes potentially involved in pharmacokinetics (ABCG2, AHR, POR and CYP1A2) and pharmacodynamics (BDNF and SLC6A4) of caffeine. Two map to GCKR and MLXIPL genes related to metabolic traits but lacking known roles in coffee consumption. Enhancer and promoter histone marks populate the regions of many confirmed loci and several potential regulatory SNPs are highly correlated with the lead SNP of each. SNP alleles near GCKR, MLXIPL, BDNF and CYP1A2 that were associated with higher coffee consumption have previously been associated with smoking initiation, higher adiposity and fasting insulin and glucose but lower blood pressure and favorable lipid, inflammatory and liver enzyme profiles (P<5 × 10(-8)).Our genetic findings among European and African-American adults reinforce the role of caffeine in mediating habitual coffee consumption and may point to molecular mechanisms underlying inter-individual variability in pharmacological and health effects of coffee.

  • 38. Dawed, A. Y.
    et al.
    Franks, Paul
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Lund Univ, Dept Clin Sci, Skane Univ Hosp, Genet & Mol Epidemiol Unit,Diabet Ctr, Malmö, Sweden; Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
    Walker, M.
    Mari, A.
    Pearson, E. R.
    Determinants of glucagon-like peptide-1 (GLP-1) response in prediabetes and diabetes: an IMI-DIRECT study2016Ingår i: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 33, nr Special Issue, Meeting Abstract: A15, s. 10-10Artikel i tidskrift (Övrigt vetenskapligt)
  • 39. Dawed, Adem Y.
    et al.
    Ali, Ashfaq
    Zhou, Kaixin
    Pearson, Ewan R.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Skåne University Hospital Malmö, Malmö, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, USA.
    Evidence-based prioritisation and enrichment of genes interacting with metformin in type 2 diabetes2017Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, nr 11, s. 2231-2239Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims/hypothesis: There is an extensive body of literature suggesting the involvement of multiple loci in regulating the action of metformin; most findings lack replication, without which distinguishing true-positive from false-positive findings is difficult. To address this, we undertook evidence-based, multiple data integration to determine the validity of published evidence. Methods: We (1) built a database of published data on gene-metformin interactions using an automated text-mining approach (n = 5963 publications), (2) generated evidence scores for each reported locus, (3) from which a rank-ordered gene set was generated, and (4) determined the extent to which this gene set was enriched for glycaemic response through replication analyses in a well-powered independent genome-wide association study (GWAS) dataset from the Genetics of Diabetes and Audit Research Tayside Study (GoDARTS). Results: From the literature search, seven genes were identified that are related to the clinical outcomes of metformin. Fifteen genes were linked with either metformin pharmacokinetics or pharmacodynamics, and the expression profiles of a further 51 genes were found to be responsive to metformin. Gene-set enrichment analysis consisting of the three sets and two more composite sets derived from the above three showed no significant enrichment in four of the gene sets. However, we detected significant enrichment of genes in the least prioritised category (a gene set in which their expression is affected by metformin) with glycaemic response to metformin (p = 0.03). This gene set includes novel candidate genes such as SLC2A4 (p = 3.24 x 10(-04)) and G6PC (p = 4.77 x 10(-04)). Conclusions/interpretation: We have described a semi-automated text-mining and evidence-scoring algorithm that facilitates the organisation and extraction of useful information about gene-drug interactions. We further validated the output of this algorithm in a drug-response GWAS dataset, providing novel candidate loci for gene-metformin interactions.

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  • 40. Dawed, Adem Y.
    et al.
    Zhou, Kaixin
    van Leeuwen, Nienke
    Mahajan, Anubha
    Robertson, Neil
    Koivula, Robert
    Elders, Petra J. M.
    Rauh, Simone P.
    Jones, Angus G.
    Holl, Reinhard W.
    Stingl, Julia C.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Skåne University Hospital, Malmö, Lund University, Malmö, Sweden; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA .
    McCarthy, Mark I.
    't Hart, Leen M.
    Pearson, Ewan R.
    Variation in the Plasma Membrane Monoamine Transporter (PMAT) (Encoded by SLC29A4) and Organic Cation Transporter 1 (OCT1) (Encoded by SLC22A1) and Gastrointestinal Intolerance to Metformin in Type 2 Diabetes: An IMI DIRECT Study2019Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 42, nr 6, s. 1027-1033Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Gastrointestinal adverse effects occur in 20-30% of patients with metformin-treated type 2 diabetes, leading to premature discontinuation in 5-10% of the cases. Gastrointestinal intolerance may reflect localized high concentrations of metformin in the gut. We hypothesized that reduced transport of metformin via the plasma membrane monoamine transporter (PMAT) and organic cation transporter 1 (OCT1) could increase the risk of severe gastrointestinal adverse effects.

    RESEARCH DESIGN AND METHODS: The study included 286 severe metformin-intolerant and 1,128 metformin-tolerant individuals from the IMI DIRECT (Innovative Medicines Initiative: DIabetes REsearCh on patient straTification) consortium. We assessed the association of patient characteristics, concomitant medication, and the burden of mutations in the SLC29A4 and SLC22A1 genes on odds of intolerance.

    RESULTS: Women (P < 0.001) and older people (P < 0.001) were more likely to develop metformin intolerance. Concomitant use of transporter-inhibiting drugs increased the odds of intolerance (odds ratio [OR] 1.72, P < 0.001). In an adjusted logistic regression model, the G allele at rs3889348 (SLC29A4) was associated with gastrointestinal intolerance (OR 1.34, P = 0.005). rs3889348 is the top cis-expression quantitative trait locus for SLC29A4 in gut tissue where carriers of the G allele had reduced expression. Homozygous carriers of the G allele treated with transporter-inhibiting drugs had more than three times higher odds of intolerance compared with carriers of no G allele and not treated with inhibiting drugs (OR 3.23, P < 0.001). Use of a genetic risk score derived from rs3889348 and SLC22A1 variants found that the odds of intolerance were more than twice as high in individuals who carry three or more risk alleles compared with those carrying none (OR 2.15, P = 0.01).

    CONCLUSIONS: These results suggest that intestinal metformin transporters and concomitant medications play an important role in the gastrointestinal adverse effects of metformin.

  • 41. de las Fuentes, Lisa
    et al.
    Schwander, Karen L.
    Brown, Michael R.
    Bentley, Amy R.
    Winkler, Thomas W.
    Sung, Yun Ju
    Munroe, Patricia B.
    Miller, Clint L.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Arnett, Donna K.
    Rao, Dabeeru C.
    Gauderman, James
    Liu, Ching-Ti
    Morrison, Alanna C.
    Rotter, Jerome I.
    Fornage, Myriam
    Gene-educational attainment interactions in a multi-population genome-wide meta-analysis identify novel lipid loci2023Ingår i: Frontiers in Genetics, E-ISSN 1664-8021, Vol. 14, artikel-id 1235337Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Educational attainment, widely used in epidemiologic studies as a surrogate for socioeconomic status, is a predictor of cardiovascular health outcomes.

    Methods: A two-stage genome-wide meta-analysis of low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride (TG) levels was performed while accounting for gene-educational attainment interactions in up to 226,315 individuals from five population groups. We considered two educational attainment variables: “Some College” (yes/no, for any education beyond high school) and “Graduated College” (yes/no, for completing a 4-year college degree). Genome-wide significant (p < 5 × 10−8) and suggestive (p < 1 × 10−6) variants were identified in Stage 1 (in up to 108,784 individuals) through genome-wide analysis, and those variants were followed up in Stage 2 studies (in up to 117,531 individuals).

    Results: In combined analysis of Stages 1 and 2, we identified 18 novel lipid loci (nine for LDL, seven for HDL, and two for TG) by two degree-of-freedom (2 DF) joint tests of main and interaction effects. Four loci showed significant interaction with educational attainment. Two loci were significant only in cross-population analyses. Several loci include genes with known or suggested roles in adipose (FOXP1, MBOAT4, SKP2, STIM1, STX4), brain (BRI3, FILIP1, FOXP1, LINC00290, LMTK2, MBOAT4, MYO6, SENP6, SRGAP3, STIM1, TMEM167A, TMEM30A), and liver (BRI3, FOXP1) biology, highlighting the potential importance of brain-adipose-liver communication in the regulation of lipid metabolism. An investigation of the potential druggability of genes in identified loci resulted in five gene targets shown to interact with drugs approved by the Food and Drug Administration, including genes with roles in adipose and brain tissue.

    Discussion: Genome-wide interaction analysis of educational attainment identified novel lipid loci not previously detected by analyses limited to main genetic effects.

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  • 42.
    de las Fuentes, Lisa
    et al.
    Cardiovascular Division, Department of Medicine, Washington University, MO, St. Louis, United States; Division of Biostatistics, Washington University School of Medicine, MO, St. Louis, United States.
    Sung, Yun Ju
    Division of Biostatistics, Washington University School of Medicine, MO, St. Louis, United States.
    Noordam, Raymond
    Section of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, Netherlands.
    Winkler, Thomas
    Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany.
    Feitosa, Mary F.
    Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, MO, St. Louis, United States.
    Schwander, Karen
    Division of Biostatistics, Washington University School of Medicine, MO, St. Louis, United States.
    Bentley, Amy R.
    Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, MD, Bethesda, United States.
    Brown, Michael R.
    Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, TX, Houston, United States.
    Guo, Xiuqing
    The Institute for Translational Genomics and Population Sciences, Division of Genomic Outcomes, Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, CA, Torrance, United States.
    Manning, Alisa
    Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, MA, Boston, United States; Department of Medicine, Harvard Medical School, MA, Boston, United States.
    Chasman, Daniel I.
    Division of Preventive Medicine, Brigham and Women’s Hospital, MA, Boston, United States; Harvard Medical School, MA, Boston, United States.
    Aschard, Hugues
    Department of Epidemiology, Harvard School of Public Health, MA, Boston, United States; Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Institut Pasteur, Paris, France.
    Bartz, Traci M.
    Cardiovascular Health Research Unit, Biostatistics and Medicine, University of Washington, WA, Seattle, United States.
    Bielak, Lawrence F.
    Department of Epidemiology, School of Public Health, University of Michigan, MI, Ann Arbor, United States.
    Campbell, Archie
    Centre for Genomic & Experimental Medicine, Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
    Cheng, Ching-Yu
    Ocular Epidemiology, Singapore Eye Research Institute, Singapore National Ecy Centre, Singapore, Singapore; Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, Singapore.
    Dorajoo, Rajkumar
    Genome Institute of Singapore, Agency for Science Technology and Research, Singapore, Singapore.
    Hartwig, Fernando P.
    Postgraduate Programme in Epidemiology, Federal University of Pelotas, RS, Pelotas, Brazil; Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
    Horimoto, A.R.V.R.
    Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School, SP, São Paulo, Brazil.
    Li, Changwei
    Epidemiology and Biostatistics, University of Georgia at Athens College of Public Health, GA, Athens, United States.
    Li-Gao, Ruifang
    Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands.
    Liu, Yongmei
    Public Health Sciences, Epidemiology and Prevention, Wake Forest University Health Sciences, NC, Winston-Salem, United States.
    Marten, Jonathan
    Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
    Musani, Solomon K.
    Jackson Heart Study, Department of Medicine, University of Mississippi Medical Center, MS, Jackson, United States.
    Ntalla, Ioanna
    Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
    Rankinen, Tuomo
    Human Genomics Laboratory, Pennington Biomedical Research Center, LA, Baton Rouge, United States.
    Richard, Melissa
    Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, TX, Houston, United States.
    Sim, Xueling
    Saw Swee Hock School of Public Health, National University Health System and National University of Singapore, Singapore, Singapore.
    Smith, Albert V.
    Department of Biostatistics, University of Michigan, MI, Ann Arbor, United States; Icelandic Heart Association, Kopavogur, Iceland.
    Tajuddin, Salman M.
    Health Disparities Research Section, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, MD, Baltimore, United States.
    Tayo, Bamidele O.
    Department of Public Health Sciences, Loyola University Chicago, IL, Maywood, United States.
    Vojinovic, Dina
    Department of Epidemiology, Erasmus University Medical Center, Rotterdam, Netherlands.
    Warren, Helen R.
    Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom; NIHR Barts Cardiovascular Biomedical Research Unit, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, London, United Kingdom.
    Xuan, Deng
    Biostatistics, Boston University School of Public Health, MA, Boston, United States.
    Alver, Maris
    Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia; Department of Biotechnology, Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
    Boissel, Mathilde
    CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, University of Lille, Lille, France.
    Chai, Jin-Fang
    Saw Swee Hock School of Public Health, National University Health System and National University of Singapore, Singapore, Singapore.
    Chen, Xu
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Stockholm, Sweden.
    Christensen, Kaare
    Unit of Epidemiology, Biostatistics and Biodemography, Department of Public Health, Southern Denmark University, Odense, Denmark.
    Divers, Jasmin
    Biostatistical Sciences, Public Health Sciences, Wake Forest School of Medicine, NC, Winston-Salem, United States.
    Evangelou, Evangelos
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom; Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece.
    Gao, Chuan
    Molecular Genetics and Genomics Program, Wake Forest School of Medicine, NC, Winston-Salem, United States.
    Girotto, Giorgia
    Medical Genetics, Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy; Institute for Maternal and Child Health–IRCCS “Burlo Garofolo”, Trieste, Italy.
    Harris, Sarah E.
    Department of Psychology, Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, United Kingdom.
    He, Meian
    Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
    Hsu, Fang-Chi
    Biostatistical Sciences, Public Health Sciences, Wake Forest School of Medicine, NC, Winston-Salem, United States.
    Kühnel, Brigitte
    Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
    Laguzzi, Federica
    Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Li, Xiaoyin
    Department of Population and Quantitative Health Sciences, Case Western Reserve University, OH, Cleveland, United States; Department of Mathematics and Statistics, University of Minnesota, MN, Duluth, United States.
    Lyytikäinen, Leo-Pekka
    Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland; Department of Clinical Chemistry, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, University of Tampere, Tampere, Finland.
    Nolte, Ilja M.
    University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, Netherlands.
    Poveda, Alaitz
    Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Skåne University Hospital, Skåne, Malmö, Sweden.
    Rauramaa, Rainer
    Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, Finland.
    Riaz, Muhammad
    College of Medicine, Biological Sciences and Psychology, Health Sciences, The Infant Mortality and Morbidity Studies (TIMMS), Leicester, United Kingdom.
    Rueedi, Rico
    Department of Computational Biology, University of Lausanne, Lausanne, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland.
    Shu, Xiao-ou
    Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, TN, Nashville, United States.
    Snieder, Harold
    University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, Netherlands.
    Sofer, Tamar
    Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital, MA, Boston, United States.
    Takeuchi, Fumihiko
    Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
    Verweij, Niek
    University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, Netherlands.
    Ware, Erin B.
    Survey Research Center, Institute for Social Research, University of Michigan, MI, Ann Arbor, United States.
    Weiss, Stefan
    Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany; DZHK (German Centre for Cardiovascular Health), Partner Site Greifswald, Greifswald, Germany.
    Yanek, Lisa R.
    Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, MD, Baltimore, United States.
    Amin, Najaf
    Department of Epidemiology, Erasmus University Medical Center, Rotterdam, Netherlands.
    Arking, Dan E.
    McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, MD, Baltimore, United States.
    Arnett, Donna K.
    Dean’s Office, University of Kentucky College of Public Health, KY, Lexington, United States.
    Bergmann, Sven
    Department of Computational Biology, University of Lausanne, Lausanne, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland.
    Boerwinkle, Eric
    Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, TX, Houston, United States; Human Genome Sequencing Center, Baylor College of Medicine, TX, Houston, United States.
    Brody, Jennifer A.
    Cardiovascular Health Research Unit, Medicine, University of Washington, WA, Seattle, United States.
    Broeckel, Ulrich
    Section of Genomic Pediatrics, Department of Pediatrics, Medicine and Physiology, Medical College of Wisconsin, WI, Milwaukee, United States.
    Brumat, Marco
    Medical Genetics, Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy.
    Burke, Gregory
    Public Health Sciences, Wake Forest School of Medicine, NC, Winston-Salem, United States.
    Cabrera, Claudia P.
    Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom; NIHR Barts Cardiovascular Biomedical Research Unit, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, London, United Kingdom.
    Canouil, Mickaël
    CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, University of Lille, Lille, France.
    Chee, Miao Li
    Statistics Unit, Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.
    Chen, Yii-Der Ida
    The Institute for Translational Genomics and Population Sciences, Division of Genomic Outcomes, Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, CA, Torrance, United States.
    Cocca, Massimiliano
    Institute for Maternal and Child Health–IRCCS “Burlo Garofolo”, Trieste, Italy.
    Connell, John
    Ninewells Hospital & Medical School, University of Dundee, Dundee, United Kingdom.
    de Silva, H. Janaka
    Department of Medicine, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka.
    de Vries, Paul S.
    Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, TX, Houston, United States.
    Eiriksdottir, Gudny
    Icelandic Heart Association, Kopavogur, Iceland.
    Faul, Jessica D.
    Survey Research Center, Institute for Social Research, University of Michigan, MI, Ann Arbor, United States.
    Fisher, Virginia
    Biostatistics, Boston University School of Public Health, MA, Boston, United States.
    Forrester, Terrence
    Tropical Metabolism Research Unit, Tropical Medicine Research Institute, University of the West Indies, Mona, Jamaica.
    Fox, Ervin F.
    Cardiology, Medicine, University of Mississippi Medical Center, MS, Jackson, United States.
    Friedlander, Yechiel
    Braun School of Public Health, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
    Gao, He
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom; MRC-PHE Centre for Environment and Health, Imperial College London, London, United Kingdom.
    Gigante, Bruna
    Cardiovascular Unit, Bioclinicum, Department of Medicine, Karolinska Hospital, Stockholm, Sweden; Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd University Hospital, Stockholm, Sweden.
    Giulianini, Franco
    Brigham and Women’s Hospital, MA, Boston, United States.
    Gu, Chi Charles
    Division of Biostatistics, Washington University School of Medicine, MO, St. Louis, United States.
    Gu, Dongfeng
    Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
    Harris, Tamara B.
    Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, MD, Bethesda, United States.
    He, Jiang
    Epidemiology, Tulane University School of Public Health and Tropical Medicine, LA, New Orleans, United States; Medicine, Tulane University School of Medicine, LA, New Orleans, United States.
    Heikkinen, Sami
    Institute of Biomedicine, School of Medicine, University of Eastern Finland, Kuopio Campus, Kuopio, Finland; Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland.
    Heng, Chew-Kiat
    Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Khoo Teck Puat – National University Children’s Medical Institute, National University Health System, Singapore, Singapore.
    Hunt, Steven
    Cardiovascular Genetics, Department of Internal Medicine, University of Utah, UT, Salt Lake City, United States; Weill Cornell Medicine in Qatar, Doha, Qatar.
    Ikram, M. Arfan
    Department of Epidemiology, Erasmus University Medical Center, Rotterdam, Netherlands; Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, Netherlands.
    Irvin, Marguerite R.
    Department of Biostatistics, University of Alabama at Birmingham, AL, Birmingham, United States.
    Kähönen, Mika
    Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland; Department of Clinical Physiology, Finnish Cardiovascular Research Center–Tampere, Faculty of Medicine and Health Technology, University of Tampere, Tampere, Finland.
    Kavousi, Maryam
    Department of Epidemiology, Erasmus University Medical Center, Rotterdam, Netherlands.
    Khor, Chiea Chuen
    Genome Institute of Singapore, Agency for Science Technology and Research, Singapore, Singapore; Department of Biochemistry, National University of Singapore, Singapore, Singapore.
    Kilpeläinen, Tuomas O.
    Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Environmental Medicine and Public Health, The Icahn School of Medicine at Mount Sinai, NY, New York, United States.
    Koh, Woon-Puay
    Saw Swee Hock School of Public Health, National University Health System and National University of Singapore, Singapore, Singapore; Health Services and Systems Research, Duke-NUS Medical School, Singapore, Singapore.
    Komulainen, Pirjo
    Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, Finland.
    Kraja, Aldi T.
    Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, MO, St. Louis, United States.
    Krieger, J.E.
    Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School, SP, São Paulo, Brazil.
    Langefeld, Carl D.
    Biostatistical Sciences, Public Health Sciences, Wake Forest School of Medicine, NC, Winston-Salem, United States.
    Li, Yize
    Division of Biostatistics, Washington University School of Medicine, MO, St. Louis, United States.
    Liang, Jingjing
    Department of Population and Quantitative Health Sciences, Case Western Reserve University, OH, Cleveland, United States.
    Liewald, David C. M.
    Department of Psychology, Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, United Kingdom.
    Liu, Ching-Ti
    Biostatistics, Boston University School of Public Health, MA, Boston, United States.
    Liu, Jianjun
    Genome Institute of Singapore, Agency for Science Technology and Research, Singapore, Singapore; Saw Swee Hock School of Public Health, National University Health System and National University of Singapore, Singapore, Singapore.
    Lohman, Kurt K.
    Public Health Sciences, Biostatistics and Data Science, Wake Forest University Health Sciences, NC, Winston-Salem, United States.
    Mägi, Reedik
    Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.
    McKenzie, Colin A.
    Tropical Metabolism Research Unit, Tropical Medicine Research Institute, University of the West Indies, Mona, Jamaica.
    Meitinger, Thomas
    Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Institute of Human Genetics, Technische Universität München, Munich, Germany.
    Metspalu, Andres
    Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia; Department of Biotechnology, Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
    Milaneschi, Yuri
    Department of Psychiatry, Amsterdam Neuroscience and Amsterdam Public Health Research Institute, VU University Medical Center, Amsterdam, Netherlands.
    Milani, Lili
    Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.
    Mook-Kanamori, Dennis O.
    Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands; Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, Netherlands.
    Nalls, Mike A.
    Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, MD, Bethesda, United States; Data Tecnica International, MD, Glen Echo, United States.
    Nelson, Christopher P.
    Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom; NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom.
    Norris, Jill M.
    Department of Epidemiology, University of Colorado Denver, CO, Aurora, United States.
    O’Connell, Jeff
    Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, MD, Baltimore, United States; Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, MD, Baltimore, United States.
    Ogunniyi, Adesola
    Department of Medicine, University of Ibadan, Oyo, Ibadan, Nigeria.
    Padmanabhan, Sandosh
    British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
    Palmer, Nicholette D.
    Biochemistry, Wake Forest School of Medicine, NC, Winston-Salem, United States.
    Pedersen, Nancy L.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Stockholm, Sweden.
    Perls, Thomas
    Department of Medicine, Geriatrics Section, Boston Medical Center, Boston University School of Medicine, MA, Boston, United States.
    Peters, Annette
    Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Neuherberg, Germany.
    Petersmann, Astrid
    Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
    Peyser, Patricia A.
    Department of Epidemiology, School of Public Health, University of Michigan, MI, Ann Arbor, United States.
    Polasek, Ozren
    University of Split School of Medicine, Split, Croatia; University Hospital Split, Split, Croatia; Psychiatric Hospital “Sveti Ivan”, Zagreb, Croatia.
    Porteous, David J.
    Centre for Genomic & Experimental Medicine, Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom; Department of Psychology, Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, United Kingdom.
    Raffel, Leslie J.
    Division of Genetic and Genomic Medicine, Department of Pediatrics, University of California, CA, Irvine, United States.
    Rice, Treva K.
    Division of Biostatistics, Washington University School of Medicine, MO, St. Louis, United States.
    Rotter, Jerome I.
    The Institute for Translational Genomics and Population Sciences, Division of Genomic Outcomes, Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, CA, Torrance, United States.
    Rudan, Igor
    Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, United Kingdom.
    Rueda-Ochoa, Oscar-Leonel
    Department of Epidemiology, Erasmus University Medical Center, Rotterdam, Netherlands.
    Sabanayagam, Charumathi
    Ocular Epidemiology, Singapore Eye Research Institute, Singapore National Ecy Centre, Singapore, Singapore; Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, Singapore.
    Salako, Babatunde L.
    Department of Medicine, University of Ibadan, Oyo, Ibadan, Nigeria.
    Schreiner, Pamela J.
    Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, MN, Minneapolis, United States.
    Shikany, James M.
    Division of Preventive Medicine, School of Medicine, University of Alabama at Birmingham, AL, Birmingham, United States.
    Sidney, Stephen S.
    Division of Research, Kaiser Permanente of Northern California, CA, Oakland, United States.
    Sims, Mario
    Jackson Heart Study, Department of Medicine, University of Mississippi Medical Center, MS, Jackson, United States.
    Sitlani, Colleen M.
    Cardiovascular Health Research Unit, Medicine, University of Washington, WA, Seattle, United States.
    Smith, Jennifer A.
    Department of Epidemiology, School of Public Health, University of Michigan, MI, Ann Arbor, United States; Survey Research Center, Institute for Social Research, University of Michigan, MI, Ann Arbor, United States.
    Starr, John M.
    Alzheimer Scotland Dementia Research Centre, The University of Edinburgh, Edinburgh, United Kingdom; Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, United Kingdom.
    Strauch, Konstantin
    Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Institute of Medical Informatics Biometry and Epidemiology, Ludwig-Maximilians-Universitat Munchen, Munich, Germany.
    Swertz, Morris A.
    University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, Netherlands.
    Teumer, Alexander
    DZHK (German Centre for Cardiovascular Health), Partner Site Greifswald, Greifswald, Germany; Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
    Tham, Yih Chung
    Ocular Epidemiology, Singapore Eye Research Institute, Singapore National Ecy Centre, Singapore, Singapore.
    Uitterlinden, André G.
    Department of Epidemiology, Erasmus University Medical Center, Rotterdam, Netherlands; Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, Netherlands.
    Vaidya, Dhananjay
    Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, MD, Baltimore, United States.
    van der Ende, M. Yldau
    University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, Netherlands.
    Waldenberger, Melanie
    Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Neuherberg, Germany.
    Wang, Lihua
    Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, MO, St. Louis, United States.
    Wang, Ya-Xing
    Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Ophthalmology and Visual Science Key Lab, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
    Wei, Wen-Bin
    Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
    Weir, David R.
    Survey Research Center, Institute for Social Research, University of Michigan, MI, Ann Arbor, United States.
    Wen, Wanqing
    Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, TN, Nashville, United States.
    Yao, Jie
    The Institute for Translational Genomics and Population Sciences, Division of Genomic Outcomes, Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, CA, Torrance, United States.
    Yu, Bing
    Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, TX, Houston, United States.
    Yu, Caizheng
    Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
    Yuan, Jian-Min
    Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, PA, Pittsburgh, United States; Division of Cancer Control and Population Sciences, UPMC Hillman Cancer, , University of Pittsburgh, PA, Pittsburgh, United States.
    Zhao, Wei
    Department of Epidemiology, School of Public Health, University of Michigan, MI, Ann Arbor, United States.
    Zonderman, Alan B.
    Behavioral Epidemiology Section, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, MD, Baltimore, United States.
    Becker, Diane M.
    Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, MD, Baltimore, United States.
    Bowden, Donald W.
    Biochemistry, Wake Forest School of Medicine, NC, Winston-Salem, United States.
    Deary, Ian J.
    Department of Psychology, Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, United Kingdom.
    Dörr, Marcus
    DZHK (German Centre for Cardiovascular Health), Partner Site Greifswald, Greifswald, Germany; Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany.
    Esko, Tõnu
    Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia; Broad Institute of the Massachusetts Institute of Technology and Harvard University, MA, Boston, United States.
    Freedman, Barry I.
    Section on Nephrology, Department of Internal Medicine, Wake Forest School of Medicine, Winston-, NC, Salem, United States.
    Froguel, Philippe
    CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, University of Lille, Lille, France; Department of Genomics of Common Disease, Imperial College London, London, United Kingdom.
    Gasparini, Paolo
    Medical Genetics, Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy; Institute for Maternal and Child Health–IRCCS “Burlo Garofolo”, Trieste, Italy.
    Gieger, Christian
    Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
    Jonas, Jost Bruno
    Department of Ophthalmology, Medical Faculty Mannheim, University Heidelberg, Mannheim, Germany; Beijing Institute of Ophthalmology, Beijing Ophthalmology and Visual Science Key Lab, Beijing Tongren Eye Center, Capital Medical University, Beijing, China.
    Kammerer, Candace M.
    Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, PA, Pittsburgh, United States.
    Kato, Norihiro
    Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
    Lakka, Timo A.
    Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, Finland; Institute of Biomedicine, School of Medicine, University of Eastern Finland, Kuopio Campus, Kuopio, Finland; Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland.
    Leander, Karin
    Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Lehtimäki, Terho
    Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland; Department of Clinical Chemistry, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, University of Tampere, Tampere, Finland.
    Magnusson, Patrik K. E.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Stockholm, Sweden.
    Marques-Vidal, Pedro
    Department of Medicine, Internal Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
    Penninx, Brenda W. J. H.
    Department of Psychiatry, Amsterdam Neuroscience and Amsterdam Public Health Research Institute, VU University Medical Center, Amsterdam, Netherlands.
    Samani, Nilesh J.
    Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom; NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom.
    van der Harst, Pim
    University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, Netherlands; Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Ultrecht, Netherlands.
    Wagenknecht, Lynne E.
    Public Health Sciences, Wake Forest School of Medicine, NC, Winston-Salem, United States.
    Wu, Tangchun
    Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
    Zheng, Wei
    Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, TN, Nashville, United States.
    Zhu, Xiaofeng
    Department of Population and Quantitative Health Sciences, Case Western Reserve University, OH, Cleveland, United States.
    Bouchard, Claude
    Human Genomics Laboratory, Pennington Biomedical Research Center, LA, Baton Rouge, United States.
    Cooper, Richard S.
    Department of Public Health Sciences, Loyola University Chicago, IL, Maywood, United States.
    Correa, Adolfo
    Jackson Heart Study, Department of Medicine, University of Mississippi Medical Center, MS, Jackson, United States.
    Evans, Michele K.
    Health Disparities Research Section, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, MD, Baltimore, United States.
    Gudnason, Vilmundur
    Icelandic Heart Association, Kopavogur, Iceland; Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
    Hayward, Caroline
    Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
    Horta, Bernardo L.
    Postgraduate Programme in Epidemiology, Federal University of Pelotas, RS, Pelotas, Brazil.
    Kelly, Tanika N.
    Epidemiology, Tulane University School of Public Health and Tropical Medicine, LA, New Orleans, United States.
    Kritchevsky, Stephen B.
    Sticht Center for Health Aging and Alzheimer’s Prevention, Department of Internal Medicine, Wake Forest School of Medicine, NC, Winston-Salem, United States.
    Levy, Daniel
    NHLBI Framingham Heart Study, MA, Framingham, United States; Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, NIH, MD, Bethesda, United States.
    Palmas, Walter R.
    Division of General Medicine, Department of Medicine, Columbia University Medical Center, NY, New York, United States.
    Pereira, A.C.
    Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School, SP, São Paulo, Brazil.
    Province, Michael M.
    Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, MO, St. Louis, United States.
    Psaty, Bruce M.
    Cardiovascular Health Research Unit, Epidemiology, Medicine and Health Services, University of Washington, WA, Seattle, United States; Kaiser Permanente Washington Health Research Institute, WA, Seattle, United States.
    Ridker, Paul M.
    Harvard Medical School, MA, Boston, United States; Brigham and Women’s Hospital, MA, Boston, United States.
    Rotimi, Charles N.
    Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, MD, Bethesda, United States.
    Tai, E. Shyong
    Saw Swee Hock School of Public Health, National University Health System and National University of Singapore, Singapore, Singapore; Health Services and Systems Research, Duke-NUS Medical School, Singapore, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
    van Dam, Rob M.
    Saw Swee Hock School of Public Health, National University Health System and National University of Singapore, Singapore, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
    van Duijn, Cornelia M.
    Department of Epidemiology, Erasmus University Medical Center, Rotterdam, Netherlands; Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
    Wong, Tien Yin
    Ocular Epidemiology, Singapore Eye Research Institute, Singapore National Ecy Centre, Singapore, Singapore; Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, Singapore.
    Rice, Kenneth
    Department of Biostatistics, University of Washington, WA, Seattle, United States.
    Gauderman, W. James
    Biostatistics, Preventive Medicine, University of Southern California, CA, Los Angeles, United States.
    Morrison, Alanna C.
    Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, TX, Houston, United States.
    North, Kari E.
    Epidemiology, University of North Carolina Gilling School of Global Public Health, NC, Chapel Hill, United States.
    Kardia, Sharon L. R.
    Department of Epidemiology, School of Public Health, University of Michigan, MI, Ann Arbor, United States.
    Caulfield, Mark J.
    Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom; NIHR Barts Cardiovascular Biomedical Research Unit, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, London, United Kingdom.
    Elliott, Paul
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom; MRC-PHE Centre for Environment and Health, Imperial College London, London, United Kingdom.
    Munroe, Patricia B.
    Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom; NIHR Barts Cardiovascular Biomedical Research Unit, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, London, United Kingdom.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Skåne University Hospital, Skåne, Malmö, Sweden.
    Rao, Dabeeru C.
    Division of Biostatistics, Washington University School of Medicine, MO, St. Louis, United States.
    Fornage, Myriam
    Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, TX, Houston, United States.
    Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci2021Ingår i: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 26, nr 6, s. 2111-2125Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, “Some College” (yes/no) and “Graduated College” (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.

  • 43. de Vries, Paul S.
    et al.
    Brown, Michael R.
    Bentley, Amy R.
    Sung, Yun J.
    Winkler, Thomas W.
    Ntalla, Ioanna
    Schwander, Karen
    Kraja, Aldi T.
    Guo, Xiuqing
    Franceschini, Nora
    Cheng, Ching-Yu
    Sim, Xueling
    Vojinovic, Dina
    Huffman, Jennifer E.
    Musani, Solomon K.
    Li, Changwei
    Feitosa, Mary F.
    Richard, Melissa A.
    Noordam, Raymond
    Aschard, Hugues
    Bartz, Traci M.
    Bielak, Lawrence F.
    Deng, Xuan
    Dorajoo, Rajkumar
    Lohman, Kurt K.
    Manning, Alisa K.
    Rankinen, Tuomo
    Smith, Albert V.
    Tajuddin, Salman M.
    Evangelou, Evangelos
    Graff, Mariaelisa
    Alver, Maris
    Boissel, Mathilde
    Chai, Jin Fang
    Chen, Xu
    Divers, Jasmin
    Gandin, Ilaria
    Gao, Chuan
    Goel, Anuj
    Hagemeijer, Yanick
    Harris, Sarah E.
    Hartwig, Fernando P.
    He, Meian
    Horimoto, Andrea R. V. R.
    Hsu, Fang-Chi
    Jackson, Anne U.
    Kasturiratne, Anuradhani
    Komulainen, Pirjo
    Kuehnel, Brigitte
    Laguzzi, Federica
    Lee, Joseph H.
    Luan, Jian'an
    Lyytikainen, Leo-Pekka
    Matoba, Nana
    Nolte, Ilja M.
    Pietzner, Maik
    Riaz, Muhammad
    Said, M. Abdullah
    Scott, Robert A.
    Sofer, Tamar
    Stancakova, Alena
    Takeuchi, Fumihiko
    Tayo, Bamidele O.
    van der Most, Peter J.
    Varga, Tibor V.
    Wang, Yajuan
    Ware, Erin B.
    Wen, Wanqing
    Yanek, Lisa R.
    Zhang, Weihua
    Zhao, Jing Hua
    Afaq, Saima
    Amin, Najaf
    Amini, Marzyeh
    Arking, Dan E.
    Aung, Tin
    Ballantyne, Christie
    Boerwinkle, Eric
    Broeckel, Ulrich
    Campbell, Archie
    Canouil, Mickael
    Charumathi, Sabanayagam
    Chen, Yii-Der Ida
    Connell, John M.
    de Faire, Ulf
    de las Fuentes, Lisa
    de Mutsert, Renee
    de Silva, H. Janaka
    Ding, Jingzhong
    Dominiczak, Anna F.
    Duan, Qing
    Eaton, Charles B.
    Eppinga, Ruben N.
    Faul, Jessica D.
    Fisher, Virginia
    Forrester, Terrence
    Franco, Oscar H.
    Friedlander, Yechiel
    Ghanbari, Mohsen
    Giulianini, Franco
    Grabe, Hans J.
    Grove, Megan L.
    Gu, C. Charles
    Harris, Tamara B.
    Heikkinen, Sami
    Heng, Chew-Kiat
    Hirata, Makoto
    Hixson, James E.
    Howard, Barbara V.
    Ikram, M. Arfan
    Jacobs, David R., Jr.
    Johnson, Craig
    Jonas, Jost Bruno
    Kammerer, Candace M.
    Katsuya, Tomohiro
    Khor, Chiea Chuen
    Kilpelainen, Tuomas O.
    Koh, Woon-Puay
    Koistinen, Heikki A.
    Kolcic, Ivana
    Kooperberg, Charles
    Krieger, Jose E.
    Kritchevsky, Steve B.
    Kubo, Michiaki
    Kuusisto, Johanna
    Lakka, Timo A.
    Langefeld, Carl D.
    Langenberg, Claudia
    Launer, Lenore J.
    Lehne, Benjamin
    Lemaitre, Rozenn N.
    Li, Yize
    Liang, Jingjing
    Liu, Jianjun
    Liu, Kiang
    Loh, Marie
    Louie, Tin
    Magi, Reedik
    Manichaikul, Ani W.
    McKenzie, Colin A.
    Meitinger, Thomas
    Metspalu, Andres
    Milaneschi, Yuri
    Milani, Lili
    Mohlke, Karen L.
    Mosley, Thomas H., Jr.
    Mukamal, Kenneth J.
    Nalls, Mike A.
    Nauck, Matthias
    Nelson, Christopher P.
    Sotoodehnia, Nona
    O'Connell, Jeff R.
    Palmer, Nicholette D.
    Pazoki, Raha
    Pedersen, Nancy L.
    Peters, Annette
    Peyser, Patricia A.
    Polasek, Ozren
    Poulter, Neil
    Raffel, Leslie J.
    Raitakari, Olli T.
    Reiner, Alex P.
    Rice, Treva K.
    Rich, Stephen S.
    Robino, Antonietta
    Robinson, Jennifer G.
    Rose, Lynda M.
    Rudan, Igor
    Schmidt, Carsten O.
    Schreiner, Pamela J.
    Scott, William R.
    Sever, Peter
    Shi, Yuan
    Sidney, Stephen
    Sims, Mario
    Smith, Blair H.
    Smith, Jennifer A.
    Snieder, Harold
    Starr, John M.
    Strauch, Konstantin
    Tan, Nicholas
    Taylor, Kent D.
    Teo, Yik Ying
    Tham, Yih Chung
    Uitterlinden, Andre G.
    van Heemst, Diana
    Vuckovic, Dragana
    Waldenberger, Melanie
    Wang, Lihua
    Wang, Yujie
    Wang, Zhe
    Wei, Wen Bin
    Williams, Christine
    Wilson, Gregory, Sr.
    Wojczynski, Mary K.
    Yao, Jie
    Yu, Bing
    Yu, Caizheng
    Yuan, Jian-Min
    Zhao, Wei
    Zonderman, Alan B.
    Becker, Diane M.
    Boehnke, Michael
    Bowden, Donald W.
    Chambers, John C.
    Deary, Ian J.
    Esko, Tonu
    Farrall, Martin
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Department of Nutrition, T. H. Chan School of Public Health, Harvard University, Boston, Massachusetts; Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Skåne University Hospital, Malmö, Sweden; Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, Medical Sciences Division, University of Oxford, Oxford, United Kingdom.
    Freedman, Barry I.
    Froguel, Philippe
    Gasparini, Paolo
    Gieger, Christian
    Horta, Bernardo L.
    Kamatani, Yoichiro
    Kato, Norihiro
    Kooner, Jaspal S.
    Laakso, Markku
    Leander, Karin
    Lehtimaki, Terho
    Magnusson, Patrik K. E.
    Penninx, Brenda
    Pereira, Alexandre C.
    Rauramaa, Rainer
    Samani, Nilesh J.
    Scott, James
    Shu, Xiao-Ou
    van der Harst, Pim
    Wagenknecht, Lynne E.
    Wang, Ya Xing
    Wareham, Nicholas J.
    Watkins, Hugh
    Weir, David R.
    Wickremasinghe, Ananda R.
    Zheng, Wei
    Elliott, Paul
    North, Kari E.
    Bouchard, Claude
    Evans, Michele K.
    Gudnason, Vilmundur
    Liu, Ching-Ti
    Liu, Yongmei
    Psaty, Bruce M.
    Ridker, Paul M.
    van Dam, Rob M.
    Kardia, Sharon L. R.
    Zhu, Xiaofeng
    Rotimi, Charles N.
    Mook-Kanamori, Dennis O.
    Fornage, Myriam
    Kelly, Tanika N.
    Fox, Ervin R.
    Hayward, Caroline
    van Duijn, Cornelia M.
    Tai, E. Shyong
    Wong, Tien Yin
    Liu, Jingmin
    Rotter, Jerome I.
    Gauderman, W. James
    Province, Michael A.
    Munroe, Patricia B.
    Rice, Kenneth
    Chasman, Daniel I.
    Cupples, L. Adrienne
    Rao, Dabeeru C.
    Morrison, Alanna C.
    Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions2019Ingår i: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 188, nr 6, s. 1033-1054Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 x 10(-6)) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 x 10(-8) using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.

  • 44. Del Gobbo, Liana C.
    et al.
    Imamura, Fumiaki
    Aslibekyan, Stella
    Marklund, Matti
    Virtanen, Jyrki K.
    Wennberg, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Yakoob, Mohammad Y.
    Chiuve, Stephanie E.
    dela Cruz, Luicito
    Frazier-Wood, Alexis C.
    Fretts, Amanda M.
    Guallar, Eliseo
    Matsumoto, Chisa
    Prem, Kiesha
    Tanaka, Tosh
    Wu, Jason H. Y.
    Zhou, Xia
    Helmer, Catherine
    Ingelsson, Erik
    Yuan, Jian-Min
    Barberger-Gateau, Pascale
    Campos, Hannia
    Chaves, Paulo H. M.
    Djousse, Luc
    Giles, Graham G.
    Gomez-Aracena, Jose
    Hodge, Allison M.
    Hu, Frank B.
    Jansson, Jan-Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Khaw, Kay-Tee
    Koh, Woon-Puay
    Lemaitre, Rozenn N.
    Lind, Lars
    Luben, Robert N.
    Rimm, Eric B.
    Riserus, Ulf
    Samieri, Cecilia
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Siscovick, David S.
    Stampfer, Meir
    Steffen, Lyn M.
    Steffen, Brian T.
    Tsai, Michael Y.
    van Dam, Rob M.
    Voutilainen, Sari
    Willett, Walter C.
    Woodward, Mark
    Mozaffarian, Dariush
    omega-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease Pooling Project of 19 Cohort Studies2016Ingår i: JAMA Internal Medicine, ISSN 2168-6106, E-ISSN 2168-6114, Vol. 176, nr 8, s. 1155-1166Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    IMPORTANCE The role of omega-3 polyunsaturated fatty acids for primary prevention of coronary heart disease (CHD) remains controversial. Most prior longitudinal studies evaluated self-reported consumption rather than biomarkers. OBJECTIVE To evaluate biomarkers of seafood-derived eicosapentaenoic acid (EPA; 20: 5 omega-3), docosapentaenoic acid (DPA; 22: 5 omega-3), and docosahexaenoic acid (DHA; 22: 6 omega-3) and plant-derived alpha-linolenic acid (ALA; 18: 3 omega-3) for incident CHD. DATA SOURCES A global consortium of 19 studies identified by November 2014. STUDY SELECTION Available prospective (cohort, nested case-control) or retrospective studies with circulating or tissue omega-3 biomarkers and ascertained CHD. DATA EXTRACTION AND SYNTHESIS Each study conducted standardized, individual-level analysis using harmonized models, exposures, outcomes, and covariates. Findings were centrally pooled using random-effects meta-analysis. Heterogeneity was examined by age, sex, race, diabetes, statins, aspirin, omega-6 levels, and FADS desaturase genes. MAIN OUTCOMES AND MEASURES Incident total CHD, fatal CHD, and nonfatal myocardial infarction (MI). RESULTS The 19 studies comprised 16 countries, 45 637 unique individuals, and 7973 total CHD, 2781 fatal CHD, and 7157 nonfatal MI events, with omega-3 measures in total plasma, phospholipids, cholesterol esters, and adipose tissue. Median age at baseline was 59 years (range, 18-97 years), and 28 660 (62.8%) were male. In continuous (per 1-SD increase) multivariable-adjusted analyses, the omega-3 biomarkers ALA, DPA, and DHA were associated with a lower risk of fatal CHD, with relative risks (RRs) of 0.91 (95% CI, 0.84-0.98) for ALA, 0.90 (95% CI, 0.85-0.96) for DPA, and 0.90 (95% CI, 0.84-0.96) for DHA. Although DPA was associated with a lower risk of total CHD (RR, 0.94; 95% CI, 0.90-0.99), ALA (RR, 1.00; 95% CI, 0.95-1.05), EPA (RR, 0.94; 95% CI, 0.87-1.02), and DHA (RR, 0.95; 95% CI, 0.91-1.00) were not. Significant associations with nonfatal MI were not evident. Associations appeared generally stronger in phospholipids and total plasma. Restricted cubic splines did not identify evidence of nonlinearity in dose responses. CONCLUSIONS AND RELEVANCE On the basis of available studies of free-living populations globally, biomarker concentrations of seafood and plant-derived omega-3 fatty acids are associated with a modestly lower incidence of fatal CHD.

  • 45. Deshmukh, Harshal A.
    et al.
    Madsen, Anne Lundager
    Vinuela, Ana
    Have, Christian Theil
    Grarup, Niels
    Tura, Andrea
    Mahajan, Anubha
    Heggie, Alison J.
    Koivula, Robert W.
    De Masi, Federico
    Tsirigos, Konstantinos K.
    Linneberg, Allan
    Drivsholm, Thomas
    Pedersen, Oluf
    Sorensen, Thorkild I. A.
    Astrup, Arne
    Gjesing, Anette A. P.
    Pavo, Imre
    Wood, Andrew R.
    Ruetten, Hartmut
    Jones, Angus G.
    Koopman, Anitra D. M.
    Cederberg, Henna
    Rutters, Femke
    Ridderstrale, Martin
    Laakso, Markku
    McCarthy, Mark, I
    Frayling, Tim M.
    Ferrannini, Ele
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, UK; Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Skåne University Hospital Malmö, Lund University, Sweden; Department of Nutrition, Harvard TH Chan School of Public Health, Boston, Massachusetts.
    Pearson, Ewan R.
    Mari, Andrea
    Hansen, Torben
    Walker, Mark
    Genome-Wide Association Analysis of Pancreatic Beta-Cell Glucose Sensitivity2021Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 106, nr 1, s. 80-90Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Context: Pancreatic beta-cell glucose sensitivity is the slope of the plasma glucose-insulin secretion relationship and is a key predictor of deteriorating glucose tolerance and development of type 2 diabetes. However, there are no large-scale studies looking at the genetic determinants of beta-cell glucose sensitivity.

    Objective: To understand the genetic determinants of pancreatic beta-cell glucose sensitivity using genome-wide meta-analysis and candidate gene studies.

    Design: We performed a genome-wide meta-analysis for beta-cell glucose sensitivity in subjects with type 2 diabetes and nondiabetic subjects from 6 independent cohorts (n = 5706). Beta-cell glucose sensitivity was calculated from mixed meal and oral glucose tolerance tests, and its associations between known glycemia-related single nucleotide polymorphisms (SNPs) and genome-wide association study (GWAS) SNPs were estimated using linear regression models.

    Results: Beta-cell glucose sensitivity was moderately heritable (h2 ranged from 34% to 55%) using SNP and family-based analyses. GWAS meta-analysis identified multiple correlated SNPs in the CDKAL1 gene and GIPR-QPCTL gene loci that reached genome-wide significance, with SNP rs2238691 in GIPR-QPCTL (P value = 2.64 × 10−9) and rs9368219 in the CDKAL1 (P value = 3.15 × 10−9) showing the strongest association with beta-cell glucose sensitivity. These loci surpassed genome-wide significance when the GWAS meta-analysis was repeated after exclusion of the diabetic subjects. After correction for multiple testing, glycemia-associated SNPs in or near the HHEX and IGF2B2 loci were also associated with beta-cell glucose sensitivity.

    Conclusion: We show that, variation at the GIPR-QPCTL and CDKAL1 loci are key determinants of pancreatic beta-cell glucose sensitivity.

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  • 46. Ding, Ming
    et al.
    Huang, Tao
    Bergholdt, Helle K. M.
    Nordestgaard, Borge G.
    Ellervik, Christina
    Qi, Lu
    Frazier-Wood, Alexis C.
    Aslibekyan, Stella
    North, Kari E.
    Voortman, Trudy
    Graff, Mariaelisa
    Smith, Caren E.
    Lai, Chao-Qiang
    Varbo, Anette
    Lemaitre, Rozenn N.
    de Jonge, Ester A. L.
    Fumeron, Frederic
    Corella, Dolores
    Wang, Carol A.
    Tjonneland, Anne
    Overvad, Kim
    Sorensen, Thorkild I. A.
    Feitosa, Mary F.
    Wojczynski, Mary K.
    Kahonen, Mika
    Ahmad, Shafqat
    Renström, Frida
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Psaty, Bruce M.
    Siscovick, David S.
    Barroso, Ines
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Hernandez, Dena
    Ferrucci, Luigi
    Bandinelli, Stefania
    Linneberg, Allan
    Sandholt, Camilla Helene
    Pedersen, Oluf
    Hansen, Torben
    Schulz, Christina-Alexandra
    Sonestedt, Emily
    Orho-Melander, Marju
    Chen, Tzu-An
    Rotter, Jerome I.
    Allison, Mathew A.
    Rich, Stephen S.
    Sorli, Jose V.
    Coltell, Oscar
    Pennell, Craig E.
    Eastwood, Peter R.
    Hofman, Albert
    Uitterlinden, Andre G.
    Zillikens, MCarola
    van Rooij, Frank J. A.
    Chu, Audrey Y.
    Rose, Lynda M.
    Ridker, Paul M.
    Viikari, Jorma
    Raitakari, Olli
    Lehtimaki, Terho
    Mikkila, Vera
    Willett, Walter C.
    Wang, Yujie
    Tucker, Katherine L.
    Ordovas, Jose M.
    Kilpelainen, Tuomas O.
    Province, Michael A.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA; Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Arnett, Donna K.
    Tanaka, Toshiko
    Toft, Ulla
    Ericso, Ulrika
    Franco, Oscar H.
    Mozaffarian, Dariush
    Hu, Frank B.
    Chasman, Daniel I.
    Dairy consumption, systolic blood pressure, and risk of hypertension: Mendelian randomization study2017Ingår i: The BMJ, E-ISSN 1756-1833, Vol. 356, artikel-id j1000Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE To examine whether previous observed inverse associations of dairy intake with systolic blood pressure and risk of hypertension were causal. DESIGN Mendelian randomization study using the single nucleotide polymorphism rs4988235 related to lactase persistence as an instrumental variable. SETTING CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium. PARTICIPANTS Data from 22 studies with 171 213 participants, and an additional 10 published prospective studies with 26 119 participants included in the observational analysis. MAIN OUTCOME MEASURES The instrumental variable estimation was conducted using the ratio of coefficients approach. Using metaanalysis, an additional eight published randomized clinical trials on the association of dairy consumption with systolic blood pressure were summarized. RESULTS Compared with the CC genotype (CC is associated with complete lactase deficiency), the CT/TT genotype (TT is associated with lactose persistence, and CT is associated with certain lactase deficiency) of LCT-13910 (lactase persistence gene) rs4988235 was associated with higher dairy consumption (0.23 (about 55 g/day), 95% confidence interval 0.17 to 0.29) serving/day; P<0.001) and was not associated with systolic blood pressure (0.31, 95% confidence interval -0.05 to 0.68 mm Hg; P=0.09) or risk of hypertension (odds ratio 1.01, 95% confidence interval 0.97 to 1.05; P=0.27). Using LCT-13910 rs4988235 as the instrumental variable, genetically determined dairy consumption was not associated with systolic blood pressure (beta=1.35, 95% confidence interval -0.28 to 2.97 mm Hg for each serving/day) or risk of hypertension (odds ratio 1.04, 0.88 to 1.24). Moreover, meta-analysis of the published clinical trials showed that higher dairy intake has no significant effect on change in systolic blood pressure for interventions over one month to 12 months (intervention compared with control groups: beta=-0.21, 95% confidence interval -0.98 to 0.57 mm Hg). In observational analysis, each serving/day increase in dairy consumption was associated with -0.11 (95% confidence interval -0.20 to -0.02 mm Hg; P=0.02) lower systolic blood pressure but not risk of hypertension (odds ratio 0.98, 0.97 to 1.00; P=0.11). CONCLUSION The weak inverse association between dairy intake and systolic blood pressure in observational studies was not supported by a comprehensive instrumental variable analysis and systematic review of existing clinical trials.

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  • 47. Do, Ron
    et al.
    Willer, Cristen J.
    Schmidt, Ellen M.
    Sengupta, Sebanti
    Gao, Chi
    Peloso, Gina M.
    Gustafsson, Stefan
    Kanoni, Stavroula
    Ganna, Andrea
    Chen, Jin
    Buchkovich, Martin L.
    Mora, Samia
    Beckmann, Jacques S.
    Bragg-Gresham, Jennifer L.
    Chang, Hsing-Yi
    Demirkan, Ayse
    Den Hertog, Heleen M.
    Donnelly, Louise A.
    Ehret, Georg B.
    Esko, Tonu
    Feitosa, Mary F.
    Ferreira, Teresa
    Fischer, Krista
    Fontanillas, Pierre
    Fraser, Ross M.
    Freitag, Daniel F.
    Gurdasani, Deepti
    Heikkila, Kauko
    Hyppoenen, Elina
    Isaacs, Aaron
    Jackson, Anne U.
    Johansson, Asa
    Johnson, Toby
    Kaakinen, Marika
    Kettunen, Johannes
    Kleber, Marcus E.
    Li, Xiaohui
    Luan, Jian'an
    Lyytikainen, Leo-Pekka
    Magnusson, Patrik K. E.
    Mangino, Massimo
    Mihailov, Evelin
    Montasser, May E.
    Mueller-Nurasyid, Martina
    Nolte, Ilja M.
    O'Connell, Jeffrey R.
    Palmer, Cameron D.
    Perola, Markus
    Petersen, Ann-Kristin
    Sanna, Serena
    Saxena, Richa
    Service, Susan K.
    Shah, Sonia
    Shungin, Dmitry
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Umeå universitet, Medicinska fakulteten, Institutionen för odontologi. Lunds universitet.
    Sidore, Carlo
    Song, Ci
    Strawbridge, Rona J.
    Surakka, Ida
    Tanaka, Toshiko
    Teslovich, Tanya M.
    Thorleifsson, Gudmar
    Van den Herik, Evita G.
    Voight, Benjamin F.
    Volcik, Kelly A.
    Waite, Lindsay L.
    Wong, Andrew
    Wu, Ying
    Zhang, Weihua
    Absher, Devin
    Asiki, Gershim
    Barroso, Ines
    Been, Latonya F.
    Bolton, Jennifer L.
    Bonnycastle, Lori L.
    Brambilla, Paolo
    Burnett, Mary S.
    Cesana, Giancarlo
    Dimitriou, Maria
    Doney, Alex S. F.
    Doering, Angela
    Elliott, Paul
    Epstein, Stephen E.
    Eyjolfsson, Gudmundur Ingi
    Gigante, Bruna
    Goodarzi, Mark O.
    Grallert, Harald
    Gravito, Martha L.
    Groves, Christopher J.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Hartikainen, Anna-Liisa
    Hayward, Caroline
    Hernandez, Dena
    Hicks, Andrew A.
    Holm, Hilma
    Hung, Yi-Jen
    Illig, Thomas
    Jones, Michelle R.
    Kaleebu, Pontiano
    Kastelein, John J. P.
    Khaw, Kay-Tee
    Kim, Eric
    Klopp, Norman
    Komulainen, Pirjo
    Kumari, Meena
    Langenberg, Claudia
    Lehtimaki, Terho
    Lin, Shih-Yi
    Lindstrom, Jaana
    Loos, Ruth J. F.
    Mach, Francois
    McArdle, Wendy L.
    Meisinger, Christa
    Mitchell, Braxton D.
    Mueller, Gabrielle
    Nagaraja, Ramaiah
    Narisu, Narisu
    Nieminen, Tuomo V. M.
    Nsubuga, Rebecca N.
    Olafsson, Isleifur
    Ong, Ken K.
    Palotie, Aarno
    Papamarkou, Theodore
    Pomilla, Cristina
    Pouta, Anneli
    Rader, Daniel J.
    Reilly, Muredach P.
    Ridker, Paul M.
    Rivadeneira, Fernando
    Rudan, Igor
    Ruokonen, Aimo
    Samani, Nilesh
    Scharnagl, Hubert
    Seeley, Janet
    Silander, Kaisa
    Stancakova, Alena
    Stirrups, Kathleen
    Swift, Amy J.
    Tiret, Laurence
    Uitterlinden, Andre G.
    van Pelt, L. Joost
    Vedantam, Sailaja
    Wainwright, Nicholas
    Wijmenga, Cisca
    Wild, Sarah H.
    Willemsen, Gonneke
    Wilsgaard, Tom
    Wilson, James F.
    Young, Elizabeth H.
    Zhao, Jing Hua
    Adair, Linda S.
    Arveiler, Dominique
    Assimes, Themistocles L.
    Bandinelli, Stefania
    Bennett, Franklyn
    Bochud, Murielle
    Boehm, Bernhard O.
    Boomsma, Dorret I.
    Borecki, Ingrid B.
    Bornstein, Stefan R.
    Bovet, Pascal
    Burnier, Michel
    Campbell, Harry
    Chakravarti, Aravinda
    Chambers, John C.
    Chen, Yii-Der Ida
    Collins, Francis S.
    Cooper, Richard S.
    Danesh, John
    Dedoussis, George
    de Faire, Ulf
    Feranil, Alan B.
    Ferrieres, Jean
    Ferrucci, Luigi
    Freimer, Nelson B.
    Gieger, Christian
    Groop, Leif C.
    Gudnason, Vilmundur
    Gyllensten, Ulf
    Hamsten, Anders
    Harris, Tamara B.
    Hingorani, Aroon
    Hirschhorn, Joel N.
    Hofman, Albert
    Hovingh, G. Kees
    Hsiung, Chao Agnes
    Humphries, Steve E.
    Hunt, Steven C.
    Hveem, Kristian
    Iribarren, Carlos
    Jarvelin, Marjo-Riitta
    Jula, Antti
    Kahonen, Mika
    Kaprio, Jaakko
    Kesaniemi, Antero
    Kivimaki, Mika
    Kooner, Jaspal S.
    Koudstaal, Peter J.
    Krauss, Ronald M.
    Kuh, Diana
    Kuusisto, Johanna
    Kyvik, Kirsten O.
    Laakso, Markku
    Lakka, Timo A.
    Lind, Lars
    Lindgren, Cecilia M.
    Martin, Nicholas G.
    Maerz, Winfried
    McCarthy, Mark I.
    McKenzie, Colin A.
    Meneton, Pierre
    Metspalu, Andres
    Moilanen, Leena
    Morris, Andrew D.
    Munroe, Patricia B.
    Njolstad, Inger
    Pedersen, Nancy L.
    Power, Chris
    Pramstaller, Peter P.
    Price, Jackie F.
    Psaty, Bruce M.
    Quertermous, Thomas
    Rauramaa, Rainer
    Saleheen, Danish
    Salomaa, Veikko
    Sanghera, Dharambir K.
    Saramies, Jouko
    Schwarz, Peter E. H.
    Sheu, Wayne H-H
    Shuldiner, Alan R.
    Siegbahn, Agneta
    Spector, Tim D.
    Stefansson, Kari
    Strachan, David P.
    Tayo, Bamidele O.
    Tremoli, Elena
    Tuomilehto, Jaakko
    Uusitupa, Matti
    van Duijn, Cornelia M.
    Vollenweider, Peter
    Wallentin, Lars
    Wareham, Nicholas J.
    Whitfield, John B.
    Wolffenbuttel, Bruce H. R.
    Altshuler, David
    Ordovas, Jose M.
    Boerwinkle, Eric
    Palmer, Colin N. A.
    Thorsteinsdottir, Unnur
    Chasman, Daniel I.
    Rotter, Jerome I.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Lunds universitet, Harvard University.
    Ripatti, Samuli
    Cupples, L. Adrienne
    Sandhu, Manjinder S.
    Rich, Stephen S.
    Boehnke, Michael
    Deloukas, Panos
    Mohlke, Karen L.
    Ingelsson, Erik
    Abecasis, Goncalo R.
    Daly, Mark J.
    Neale, Benjamin M.
    Kathiresan, Sekar
    Common variants associated with plasma triglycerides and risk for coronary artery disease2013Ingår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 45, nr 11, s. 1345-+Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.

  • 48. Donnelly, Louise A.
    et al.
    Zhou, Kaixin
    Doney, Alex S. F.
    Jennison, Chris
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Department of Clinical Science, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, USA.
    Pearson, Ewan R.
    Rates of glycaemic deterioration in a real-world population with type 2 diabetes2018Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, nr 3, s. 607-615Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims/hypothesis: There is considerable variability in how diabetes progresses after diagnosis. Progression modelling has largely focused on 'time to failure' methods, yet determining a 'coefficient of failure' has many advantages. We derived a rate of glycaemic deterioration in type 2 diabetes, using a large real-world cohort, and aimed to investigate the clinical, biochemical, pharmacological and immunological variables associated with fast and slow rates of glycaemic deterioration. Methods: An observational cohort study was performed using the electronic medical records from participants in the Genetics of Diabetes Audit and Research in Tayside Study (GoDARTS). A model was derived based on an individual's observed HbA(1c) measures from the first eligible HbA(1c) after the diagnosis of diabetes through to the study end (defined as insulin initiation, death, leaving the area or end of follow-up). Each HbA(1c) measure was time-dependently adjusted for the effects of non-insulin glucose-lowering drugs, changes in BMI and corticosteroid use. GAD antibody (GADA) positivity was defined as GAD titres above the 97.5th centile of the population distribution. Results: The mean (95% CI) glycaemic deterioration for type 2 diabetes and GADA-positive individuals was 1.4 (1.3, 1.4) and 2.8 (2.4, 3.3) mmol/mol HbA(1c) per year, respectively. A younger age of diagnosis, lower HDL-cholesterol concentration, higher BMI and earlier calendar year of diabetes diagnosis were independently associated with higher rates of glycaemic deterioration in individuals with type 2 diabetes. The rate of deterioration in those diagnosed at over 70 years of age was very low, with 66% having a rate of deterioration of less than 1.1 mmol/mol HbA(1c) per year, and only 1.5% progressing more rapidly than 4.4 mmol/mol HbA(1c) per year. Conclusions/interpretation: We have developed a novel approach for modelling the progression of diabetes in observational data across multiple drug combinations. This approach highlights how glycaemic deterioration in those diagnosed at over 70 years of age is minimal, supporting a stratified approach to diabetes management.

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  • 49. Dudding, Tom
    et al.
    Haworth, Simon
    Lind, Penelope A.
    Sathirapongsasuti, J. Fah
    Tung, Joyce Y.
    Mitchell, Ruth
    Colodro-Conde, Lucia
    Medland, Sarah E.
    Gordon, Scott
    Elsworth, Benjamin
    Paternoster, Lavinia
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Lund University, Sweden ; Department of Nutrition, Harvard. Chan School of Public Health, Harvard University, Boston USA.
    Thomas, Steven J.
    Martin, Nicholas G.
    Timpson, Nicholas J.
    Agee, Michelle
    Alipanahi, Babak
    Auton, Adam
    Bell, Robert K.
    Bryc, Katarzyna
    Elson, Sarah L.
    Fontanillas, Pierre
    Furlotte, Nicholas A.
    Hicks, Barry
    Hinds, David A.
    Huber, Karen E.
    Jewett, Ethan M.
    Jiang, Yunxuan
    Kleinman, Aaron
    Lin, Keng-Han
    Litterman, Nadia K.
    McCeight, Jennifer C.
    McIntyre, Matthew H.
    McManus, Kimberly F.
    Mountain, Joanna L.
    Noblin, Elizabeth S.
    Northover, Carrie A. M.
    Pitts, Steven J.
    Poznik, David
    Shelton, Janie F.
    Shringarpure, Suyash
    Tian, Chao
    Vacic, Vladimir
    Wang, Xin
    Wilson, Catherine H.
    Genome wide analysis for mouth ulcers identifies associations at immune regulatory loci2019Ingår i: Nature Communications, E-ISSN 2041-1723, Vol. 10, s. 1-12, artikel-id 1052Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Mouth ulcers are the most common ulcerative condition and encompass several clinical diagnoses, including recurrent aphthous stomatitis (RAS). Despite previous evidence for heritability, it is not clear which specific genetic loci are implicated in RAS. In this genome-wide association study (n = 461,106) heritability is estimated at 8.2% (95% CI: 6.4%, 9.9%). This study finds 97 variants which alter the odds of developing non-specific mouth ulcers and replicate these in an independent cohort (n = 355,744) (lead variant after meta-analysis: rs76830965, near IL12A, OR 0.72 (95% CI: 0.71, 0.73); P = 4.4e-483). Additional effect estimates from three independent cohorts with more specific phenotyping and specific study characteristics support many of these findings. In silico functional analyses provide evidence for a role of T cell regulation in the aetiology of mouth ulcers. These results provide novel insight into the pathogenesis of a common, important condition.

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  • 50. Dupuis, Josée
    et al.
    Langenberg, Claudia
    Prokopenko, Inga
    Saxena, Richa
    Soranzo, Nicole
    Jackson, Anne U
    Wheeler, Eleanor
    Glazer, Nicole L
    Bouatia-Naji, Nabila
    Gloyn, Anna L
    Lindgren, Cecilia M
    Mägi, Reedik
    Morris, Andrew P
    Randall, Joshua
    Johnson, Toby
    Elliott, Paul
    Rybin, Denis
    Thorleifsson, Gudmar
    Steinthorsdottir, Valgerdur
    Henneman, Peter
    Grallert, Harald
    Dehghan, Abbas
    Hottenga, Jouke Jan
    Franklin, Christopher S
    Navarro, Pau
    Song, Kijoung
    Goel, Anuj
    Perry, John R B
    Egan, Josephine M
    Lajunen, Taina
    Grarup, Niels
    Sparsø, Thomas
    Doney, Alex
    Voight, Benjamin F
    Stringham, Heather M
    Li, Man
    Kanoni, Stavroula
    Shrader, Peter
    Cavalcanti-Proença, Christine
    Kumari, Meena
    Qi, Lu
    Timpson, Nicholas J
    Gieger, Christian
    Zabena, Carina
    Rocheleau, Ghislain
    Ingelsson, Erik
    An, Ping
    O'Connell, Jeffrey
    Luan, Jian'an
    Elliott, Amanda
    McCarroll, Steven A
    Payne, Felicity
    Roccasecca, Rosa Maria
    Pattou, François
    Sethupathy, Praveen
    Ardlie, Kristin
    Ariyurek, Yavuz
    Balkau, Beverley
    Barter, Philip
    Beilby, John P
    Ben-Shlomo, Yoav
    Benediktsson, Rafn
    Bennett, Amanda J
    Bergmann, Sven
    Bochud, Murielle
    Boerwinkle, Eric
    Bonnefond, Amélie
    Bonnycastle, Lori L
    Borch-Johnsen, Knut
    Böttcher, Yvonne
    Brunner, Eric
    Bumpstead, Suzannah J
    Charpentier, Guillaume
    Chen, Yii-Der Ida
    Chines, Peter
    Clarke, Robert
    Coin, Lachlan J M
    Cooper, Matthew N
    Cornelis, Marilyn
    Crawford, Gabe
    Crisponi, Laura
    Day, Ian N M
    de Geus, Eco J C
    Delplanque, Jerome
    Dina, Christian
    Erdos, Michael R
    Fedson, Annette C
    Fischer-Rosinsky, Antje
    Forouhi, Nita G
    Fox, Caroline S
    Frants, Rune
    Franzosi, Maria Grazia
    Galan, Pilar
    Goodarzi, Mark O
    Graessler, Jürgen
    Groves, Christopher J
    Grundy, Scott
    Gwilliam, Rhian
    Gyllensten, Ulf
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Hadjadj, Samy
    Hammond, Naomi
    Han, Xijing
    Hartikainen, Anna-Liisa
    Hassanali, Neelam
    Hayward, Caroline
    Heath, Simon C
    Hercberg, Serge
    Herder, Christian
    Hicks, Andrew A
    Hillman, David R
    Hingorani, Aroon D
    Hofman, Albert
    Hui, Jennie
    Hung, Joe
    Isomaa, Bo
    Johnson, Paul R V
    Jørgensen, Torben
    Jula, Antti
    Kaakinen, Marika
    Kaprio, Jaakko
    Kesaniemi, Y Antero
    Kivimaki, Mika
    Knight, Beatrice
    Koskinen, Seppo
    Kovacs, Peter
    Kyvik, Kirsten Ohm
    Lathrop, G Mark
    Lawlor, Debbie A
    Le Bacquer, Olivier
    Lecoeur, Cécile
    Li, Yun
    Lyssenko, Valeriya
    Mahley, Robert
    Mangino, Massimo
    Manning, Alisa K
    Martínez-Larrad, María Teresa
    McAteer, Jarred B
    McCulloch, Laura J
    McPherson, Ruth
    Meisinger, Christa
    Melzer, David
    Meyre, David
    Mitchell, Braxton D
    Morken, Mario A
    Mukherjee, Sutapa
    Naitza, Silvia
    Narisu, Narisu
    Neville, Matthew J
    Oostra, Ben A
    Orrù, Marco
    Pakyz, Ruth
    Palmer, Colin N A
    Paolisso, Giuseppe
    Pattaro, Cristian
    Pearson, Daniel
    Peden, John F
    Pedersen, Nancy L
    Perola, Markus
    Pfeiffer, Andreas F H
    Pichler, Irene
    Polasek, Ozren
    Posthuma, Danielle
    Potter, Simon C
    Pouta, Anneli
    Province, Michael A
    Psaty, Bruce M
    Rathmann, Wolfgang
    Rayner, Nigel W
    Rice, Kenneth
    Ripatti, Samuli
    Rivadeneira, Fernando
    Roden, Michael
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Sandbaek, Annelli
    Sandhu, Manjinder
    Sanna, Serena
    Sayer, Avan Aihie
    Scheet, Paul
    Scott, Laura J
    Seedorf, Udo
    Sharp, Stephen J
    Shields, Beverley
    Sigurethsson, Gunnar
    Sijbrands, Eric J G
    Silveira, Angela
    Simpson, Laila
    Singleton, Andrew
    Smith, Nicholas L
    Sovio, Ulla
    Swift, Amy
    Syddall, Holly
    Syvänen, Ann-Christine
    Tanaka, Toshiko
    Thorand, Barbara
    Tichet, Jean
    Tönjes, Anke
    Tuomi, Tiinamaija
    Uitterlinden, André G
    van Dijk, Ko Willems
    van Hoek, Mandy
    Varma, Dhiraj
    Visvikis-Siest, Sophie
    Vitart, Veronique
    Vogelzangs, Nicole
    Waeber, Gérard
    Wagner, Peter J
    Walley, Andrew
    Walters, G Bragi
    Ward, Kim L
    Watkins, Hugh
    Weedon, Michael N
    Wild, Sarah H
    Willemsen, Gonneke
    Witteman, Jaqueline C M
    Yarnell, John W G
    Zeggini, Eleftheria
    Zelenika, Diana
    Zethelius, Björn
    Zhai, Guangju
    Zhao, Jing Hua
    Zillikens, M Carola
    Borecki, Ingrid B
    Loos, Ruth J F
    Meneton, Pierre
    Magnusson, Patrik K E
    Nathan, David M
    Williams, Gordon H
    Hattersley, Andrew T
    Silander, Kaisa
    Salomaa, Veikko
    Smith, George Davey
    Bornstein, Stefan R
    Schwarz, Peter
    Spranger, Joachim
    Karpe, Fredrik
    Shuldiner, Alan R
    Cooper, Cyrus
    Dedoussis, George V
    Serrano-Ríos, Manuel
    Morris, Andrew D
    Lind, Lars
    Palmer, Lyle J
    Hu, Frank B
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Ebrahim, Shah
    Marmot, Michael
    Kao, W H Linda
    Pankow, James S
    Sampson, Michael J
    Kuusisto, Johanna
    Laakso, Markku
    Hansen, Torben
    Pedersen, Oluf
    Pramstaller, Peter Paul
    Wichmann, H Erich
    Illig, Thomas
    Rudan, Igor
    Wright, Alan F
    Stumvoll, Michael
    Campbell, Harry
    Wilson, James F
    Bergman, Richard N
    Buchanan, Thomas A
    Collins, Francis S
    Mohlke, Karen L
    Tuomilehto, Jaakko
    Valle, Timo T
    Altshuler, David
    Rotter, Jerome I
    Siscovick, David S
    Penninx, Brenda W J H
    Boomsma, Dorret I
    Deloukas, Panos
    Spector, Timothy D
    Frayling, Timothy M
    Ferrucci, Luigi
    Kong, Augustine
    Thorsteinsdottir, Unnur
    Stefansson, Kari
    van Duijn, Cornelia M
    Aulchenko, Yurii S
    Cao, Antonio
    Scuteri, Angelo
    Schlessinger, David
    Uda, Manuela
    Ruokonen, Aimo
    Jarvelin, Marjo-Riitta
    Waterworth, Dawn M
    Vollenweider, Peter
    Peltonen, Leena
    Mooser, Vincent
    Abecasis, Goncalo R
    Wareham, Nicholas J
    Sladek, Robert
    Froguel, Philippe
    Watanabe, Richard M
    Meigs, James B
    Groop, Leif
    Boehnke, Michael
    McCarthy, Mark I
    Florez, Jose C
    Barroso, Inês
    New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk2010Ingår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 42, nr 2, s. 105-116Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.

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