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  • 201.
    Shungin, Dmitry
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; .
    Hawort, Simon
    Divaris, Kimon
    Agler, Cary S.
    Kamatani, Yoichiro
    Lee, Myoung Keun
    Grinde, Kelsey
    Hindy, George
    Alaraudanjoki, Viivi
    Pesonen, Paula
    Teumer, Alexander
    Holtfreter, Birte
    Sakaue, Saori
    Hirata, Jun
    Yu, Yau-Hua
    Ridker, Paul M.
    Giulianini, Franco
    Chasman, Daniel, I
    Magnusson, Patrik K. E.
    Sudo, Takeaki
    Okada, Yukinori
    Voelker, Uwe
    Kocher, Thomas
    Anttonen, Vuokko
    Laitala, Marja-Liisa
    Orho-Melander, Marju
    Sofer, Tamar
    Shaffer, John R.
    Vieira, Alexandre
    Marazita, Mary L.
    Kubo, Michiaki
    Furuichi, Yasushi
    North, Kari E.
    Offenbacher, Steve
    Ingelsson, Erik
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö SE-214 28, Sweden; Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.
    Timpson, Nicholas J.
    Johansson, Ingegerd
    Genome-wide analysis of dental caries and periodontitis combining clinical and self-reported data2019Ingår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 10, artikel-id 2773Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Dental caries and periodontitis account for a vast burden of morbidity and healthcare spending, yet their genetic basis remains largely uncharacterized. Here, we identify self-reported dental disease proxies which have similar underlying genetic contributions to clinical disease measures and then combine these in a genome-wide association study meta-analysis, identifying 47 novel and conditionally-independent risk loci for dental caries. We show that the heritability of dental caries is enriched for conserved genomic regions and partially overlapping with a range of complex traits including smoking, education, personality traits and metabolic measures. Using cardio-metabolic traits as an example in Mendelian randomization analysis, we estimate causal relationships and provide evidence suggesting that the processes contributing to dental caries may have undesirable downstream effects on health.

  • 202. Sluijs, Ivonne
    et al.
    Forouhi, Nita G
    Beulens, Joline WJ
    van der Schouw, Yvonne T
    Agnoli, Claudia
    Arriola, Larraitz
    Balkau, Beverley
    Barricarte, Aurelio
    Boeing, Heiner
    Bueno-de-Mesquita, H Bas
    Clavel-Chapelon, Francoise
    Crowe, Francesca L
    de Lauzon-Guillain, Blandine
    Drogan, Dagmar
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Gavrila, Diana
    Gonzalez, Carlos
    Halkjaer, Jytte
    Kaaks, Rudolf
    Moskal, Aurelie
    Nilsson, Peter
    Overvad, Kim
    Palli, Domenico
    Panico, Salvatore
    Quiros, Jose R
    Ricceri, Fulvio
    Rinaldi, Sabina
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Sacerdote, Carlotta
    Sanchez, Maria-Jose
    Slimani, Nadia
    Spijkerman, Annemieke MW
    Teucher, Birgit
    Tjonneland, Anne
    Tormo, Maria-Jose
    Tumino, Rosario
    van der A, Daphne L
    Sharp, Stephen J
    Langenberg, Claudia
    Feskens, Edith JM
    Riboli, Elio
    Wareham, Nicholas J
    The amount and type of dairy product intake and incident type 2 diabetes: results from the EPIC-InterAct Study2012Ingår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 96, nr 2, s. 382-390Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Dairy product intake may be inversely associated with risk of type 2 diabetes, but the evidence is inconclusive for total dairy products and sparse for types of dairy products.

    Objective: The objective was to investigate the prospective association of total dairy products and different dairy subtypes with incidence of diabetes in populations with marked variation of intake of these food groups.

    Design: A nested case-cohort within 8 European countries of the European Prospective Investigation into Cancer and Nutrition Study (n = 340,234; 3.99 million person-years of follow-up) included a random subcohort (n = 16,835) and incident diabetes cases (n = 12,403). Baseline dairy product intake was assessed by using dietary questionnaires. Country-specific Prentice-weighted Cox regression HRs were calculated and pooled by using a random-effects meta-analysis.

    Results: Intake of total dairy products was not associated with diabetes (HR for the comparison of the highest with the lowest quintile of total dairy products: 1.01; 95% CI: 0.83, 1.34; P-trend = 0.92) in an analysis adjusted for age, sex, BMI, diabetes risk factors, education, and dietary factors. Of the dairy subtypes, cheese intake tended to have an inverse association with diabetes (HR: 0.88; 95% CI: 0.76, 1.02; P-trend = 0.01), and a higher combined intake of fermented dairy products (cheese, yogurt, and thick fermented milk) was inversely associated with diabetes (HR: 0.88; 95% CI: 0.78, 0.99; P-trend = 0.02) in adjusted analyses that compared extreme quintiles.

    Conclusions: This large prospective study found no association between total dairy product intake and diabetes risk. An inverse association of cheese intake and combined fermented dairy product intake with diabetes is suggested, which merits further study. Ant J Clin Nutr 2012;96:382-90.

  • 203. Sluijs, Ivonne
    et al.
    Holmes, Michael V.
    van der Schouw, Yvonne T.
    Beulens, Joline W. J.
    Asselbergs, Folkert W.
    Maria Huerta, Jose
    Palmer, Tom M.
    Arriola, Larraitz
    Balkau, Beverley
    Barricarte, Aurelio
    Boeing, Heiner
    Clavel-Chapelon, Francoise
    Fagherazzi, Guy
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Gavrila, Diana
    Kaaks, Rudolf
    Khaw, Kay Tee
    Kuehn, Tilman
    Molina-Montes, Esther
    Mortensen, Lotte Maxild
    Nilsson, Peter M.
    Overvad, Kim
    Palli, Domenico
    Panico, Salvatore
    Ramon Quiros, J.
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Sacerdote, Carlotta
    Sala, Nuria
    Schmidt, Julie A.
    Scott, Robert A.
    Sieri, Sabina
    Slimani, Nadia
    Spijkerman, Annemieke M. W.
    Tjonneland, Anne
    Travis, Ruth C.
    Tumino, Rosario
    Daphne, L. van der A.
    Sharp, Stephen J.
    Forouhi, Nita G.
    Langenberg, Claudia
    Riboli, Elio
    Wareham, Nicholas J.
    A Mendelian Randomization Study of Circulating Uric Acid and Type 2 Diabetes2015Ingår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 64, nr 8, s. 3028-3036Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We aimed to investigate the causal effect of circulating uric acid concentrations on type 2 diabetes risk. A Mendelian randomization study was performed using a genetic score with 24 uric acid-associated loci. We used data of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study, comprising 24,265 individuals of European ancestry from eight European countries. During a mean (SD) follow-up of 10 (4) years, 10,576 verified incident case subjects with type 2 diabetes were ascertained. Higher uric acid was associated with a higher diabetes risk after adjustment for confounders, with a hazard ratio (HR) of 1.20 (95% CI 1.11, 1.30) per 59.48 mu mol/L (1mg/dL) uric acid. The genetic score raised uric acid by 17 mu mol/L (95% CI 15, 18) per SD increase and explained 4% of uric acid variation. By using the genetic score to estimate the unconfounded effect, we found that a 59.48 mu mol/L higher uric acid concentration did not have a causal effect on diabetes (HR 1.01 [95% CI 0.87, 1.16]). Including data from the Diabetes Genetics Replication And Meta-analysis (DIAGRAM) consortium, increasing our dataset to 41,508 case subjects with diabetes, the summary odds ratio estimate was 0.99 (95% CI 0.92, 1.06). In conclusion, our study does not support a causal effect of circulating uric acid on diabetes risk. Uric acid-lowering therapies may therefore not be beneficial in reducing diabetes risk.

  • 204. Sluik, Diewertje
    et al.
    Boeing, Heiner
    Bergmann, Manuela M
    Schütze, Madlen
    Teucher, Birgit
    Kaaks, Rudolf
    Tjønneland, Anne
    Overvad, Kim
    Arriola, Larraitz
    Ardanaz, Eva
    Bendinelli, Benedetta
    Agnoli, Claudia
    Tumino, Rosario
    Ricceri, Fulvio
    Mattiello, Amalia
    Spijkerman, Annemieke M W
    Beulens, Joline W J
    Grobbee, Diederick E
    Nilsson, Peter M
    Melander, Olle
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Riboli, Elio
    Gallo, Valentina
    Romaguera, Dora
    Nöthlings, Ute
    Alcohol consumption and mortality in individuals with diabetes mellitus2012Ingår i: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 108, nr 7, s. 1307-1315Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Studies have suggested that moderate alcohol consumption is associated with a reduced risk of CVD and premature mortality in individuals with diabetes mellitus. However, history of alcohol consumption has hardly been taken into account. We investigated the association between current alcohol consumption and mortality in men and women with diabetes mellitus accounting for past alcohol consumption. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), a cohort was defined of 4797 participants with a confirmed diagnosis of diabetes mellitus. Men and women were assigned to categories of baseline and past alcohol consumption. Hazard ratios (HR) and 95 % CI for total mortality were estimated with multivariable Cox regression models, using light alcohol consumption (>0-6 g/d) as the reference category. Compared with light alcohol consumption, no relationship was observed between consumption of 6 g/d or more and total mortality. HR for >6-12 g/d was 0·89 (95 % CI 0·61, 1·30) in men and 0·86 (95 % CI 0·46, 1·60) in women. Adjustment for past alcohol consumption did not change the estimates substantially. In individuals who at baseline reported abstaining from alcohol, mortality rates were increased relative to light consumers: HR was 1·52 (95 % CI 0·99, 2·35) in men and 1·81 (95 % CI 1·04, 3·17) in women. The present study in diabetic individuals showed no association between current alcohol consumption >6 g/d and mortality risk compared with light consumption. The increased mortality risk among non-consumers appeared to be affected by their past alcohol consumption rather than their current abstinence.

  • 205. Sluik, Diewertje
    et al.
    Boeing, Heiner
    Montonen, Jukka
    Kaaks, Rudolf
    Lukanova, Annekatrin
    Sandbaek, Annelli
    Overvad, Kim
    Arriola, Larraitz
    Ardanaz, Eva
    Saieva, Calogero
    Grioni, Sara
    Tumino, Rosario
    Sacerdote, Carlotta
    Mattiello, Amalia
    Spijkerman, Annemieke M. W.
    van der A, Daphne L.
    Beulens, Joline W. J.
    van Dieren, Susan
    Nilsson, Peter M.
    Groop, Leif C.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Bueno-de-Mesquita, Bas
    Noethlings, Ute
    HbA(1c) Measured in Stored Erythrocytes Is Positively Linearly Associated with Mortality in Individuals with Diabetes Mellitus2012Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 6, s. e38877-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Observational studies have shown that glycated haemoglobin (HbA(1c)) is related to mortality, but the shape of the association is less clear. Furthermore, disease duration and medication may modify this association. This observational study explored the association between HbA(1c) measured in stored erythrocytes and mortality. Secondly, it was assessed whether disease duration and medication use influenced the estimates or were independently associated with mortality. Methods: Within the European Prospective Investigation into Cancer and Nutrition a cohort was analysed of 4,345 individuals with a confirmed diagnosis of diabetes at enrolment. HbA(1c) was measured in blood samples stored up to 19 years. Multivariable Cox proportional hazard regression models for all-cause mortality investigated HbA(1c) in quartiles as well as per 1% increment, diabetes medication in seven categories of insulin and oral hypoglycaemic agents, and disease duration in quartiles. Results: After a median follow-up of 9.3 years, 460 participants died. Higher HbA(1c) was associated with higher mortality: Hazard Ratio for 1%-increase was 1.11 (95% CI 1.06, 1.17). This association was linear (P-nonlinearity = 0.15) and persistent across categories of medication use, disease duration, and co-morbidities. Compared with metformin, other medication types were not associated with mortality. Longer disease duration was associated with mortality, but not after adjustment for HbA(1c) and medication. Conclusion: This prospective study showed that persons with lower HbA(1c) had better survival than those with higher HbA(1c). The association was linear and independent of disease duration, type of medication use, and presence of co-morbidities. Any improvement of HbA(1c) appears to be associated with reduced mortality risk.

  • 206. Sluik, Diewertje
    et al.
    Boeing, Heiner
    Montonen, Jukka
    Pischon, Tobias
    Kaaks, Rudolf
    Teucher, Birgit
    Tjønneland, Anne
    Halkjaer, Jytte
    Berentzen, Tina L
    Overvad, Kim
    Arriola, Larraitz
    Ardanaz, Eva
    Bendinelli, Benedetta
    Grioni, Sara
    Tumino, Rosario
    Sacerdote, Carlotta
    Mattiello, Amalia
    Spijkerman, Annemieke MW
    van der A, Daphne L
    Beulens, Joline W
    van der Schouw, Yvonne T
    Nilsson, Peter M
    Hedblad, Bo
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Nöthlings, Ute
    Associations between general and abdominal adiposity and mortality in individuals with diabetes mellitus2011Ingår i: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 174, nr 1, s. 22-34Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Individuals with diabetes mellitus are advised to achieve a healthy weight to prevent complications. However, fat mass distribution has hardly been investigated as a risk factor for diabetes complications. The authors studied associations between body mass index, waist circumference, waist/hip ratio, and waist/height ratio and mortality among individuals with diabetes mellitus. Within the European Prospective Investigation into Cancer and Nutrition, a subcohort was defined as 5,435 individuals with a confirmed self-report of diabetes mellitus at baseline in 1992-2000. Participants were aged 57.3 (standard deviation, 6.3) years, 54% were men, the median diabetes duration was 4.6 (interquartile range, 2.0-9.8) years, and 22% of the participants used insulin. Body mass index, as indicator of general obesity, was not associated with higher mortality, whereas all measurements of abdominal obesity showed a positive association. Associations generally were slightly weaker in women. The strongest association was observed for waist/height ratio: In the fifth quintile, the hazard rate ratio was 1.88 (95% confidence interval: 1.33, 2.65) for men and 2.46 (95% confidence interval: 1.46, 4.14) for women. Measurements of abdominal, but not general, adiposity were associated with higher mortality in diabetic individuals. The waist/height ratio showed the strongest association. Respective indicators might be investigated in risk prediction models.

  • 207. Spijkerman, Annemieke M. W.
    et al.
    van der A, Daphne L.
    Nilsson, Peter M.
    Ardanaz, Eva
    Gavrila, Diana
    Agudo, Antonio
    Arriola, Larraitz
    Balkau, Beverley
    Beulens, Joline W.
    Boeing, Heiner
    de Lauzon-Guillain, Blandine
    Fagherazzi, Guy
    Feskens, Edith J. M.
    Franks, Paul
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Grioni, Sara
    Huerta, Jose Maria
    Kaaks, Rudolf
    Key, Timothy J.
    Overvad, Kim
    Palli, Domenico
    Panico, Salvatore
    Redondo, M. Luisa
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Roswal, Nina
    Sacerdote, Carlotta
    Sanchez, Maria-Jose
    Schulze, Matthias B.
    Slimani, Nadia
    Teucher, Birgit
    Tjonneland, Anne
    Tumino, Rosario
    van der Schouw, Yvonne T.
    Langenberg, Claudia
    Sharp, Stephen J.
    Forouhi, Nita G.
    Riboli, Elio
    Wareham, Nicholas J.
    Smoking and Long-Term Risk of Type 2 Diabetes: The EPIC-InterAct Study in European Populations2014Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 37, nr 12, s. 3164-3171Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE

    The aims of this study were to investigate the association between smoking and incident type 2 diabetes, accounting for a large number of potential confounding factors, and to explore potential effect modifiers and intermediate factors.

    RESEARCH DESIGN AND METHODS

    The European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct is a prospective case-cohort study within eight European countries, including 12,403 cases of incident type 2 diabetes and a random subcohort of 16,835 individuals. After exclusion of individuals with missing data, the analyses included 10,327 cases and 13,863 subcohort individuals. Smoking status was used (never, former, current), with never smokers as the reference. Country-specific Prentice-weighted Cox regression models and random-effects meta-analysis were used to estimate hazard ratios (HRs) for type 2 diabetes.

    RESULTS

    In men, the HRs (95% CI) of type 2 diabetes were 1.40 (1.26, 1.55) for former smokers and 1.43 (1.27, 1.61) for current smokers, independent of age, education, center, physical activity, and alcohol, coffee, and meat consumption. In women, associations were weaker, with HRs (95% CI) of 1.18 (1.07, 1.30) and 1.13 (1.03, 1.25) for former and current smokers, respectively. There was some evidence of effect modification by BMI. The association tended to be slightly stronger in normal weight men compared with those with overall adiposity.

    CONCLUSIONS

    Former and current smoking was associated with a higher risk of incident type 2 diabetes compared with never smoking in men and women, independent of educational level, physical activity, alcohol consumption, and diet. Smoking may be regarded as a modifiable risk factor for type 2 diabetes, and smoking cessation should be encouraged for diabetes prevention.

  • 208. Stijnen, Pieter
    et al.
    Tuand, Krizia
    Varga, Tibor V.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden; Skane Univ Hosp Malmo, Malmo, Sweden; Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
    Aertgeerts, Bert
    Creemers, John W. M.
    RE: "The Association of Common Variants in PCSK1 With Obesity: A HuGE Review and Meta-Analysis" REPLY2015Ingår i: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 181, nr 9, s. 733-735Artikel i tidskrift (Refereegranskat)
  • 209. Stijnen, Pieter
    et al.
    Tuand, Krizia
    Varga, Tibor V.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Aertgeerts, Bert
    Creemers, John W. M.
    The Association of Common Variants in PCSK1 With Obesity: A HuGE Review and Meta-Analysis2014Ingår i: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 180, nr 11, s. 1051-1065Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Congenital deficiency of the proprotein convertase subtilisine/kexin type 1 gene (PCSK1), which encodes proprotein convertase 1/3, causes a severe multihormonal disorder marked by early-onset obesity. The single nucleotide polymorphisms (SNPs) rs6232 and rs6234-rs6235 in PCSK1 have been associated with obesity. However, case-control studies carried out in populations of different ethnicities have only partly replicated this association. Moreover, these SNPs have only weakly been associated with body mass index (weight (kg)/height (m)(2)) at a genome-wide level of significance. To investigate this discrepancy, we conducted a systematic search for studies published before December 2013 and extracted relevant data. Pooled estimates were calculated for overall and subgroup analyses. This meta-analysis confirmed the association of PCSK1 SNPs with obesity and provides the first evidence that the association between PCSK1 rs6232 and obesity is stronger for childhood obesity than for adult obesity. Moreover, we identified weak associations with body mass index and significantly stronger associations with waist circumference for rs6234-rs6235. No difference was found in the association with different obesity grades, and no association of PCSK1 rs6234-rs6235 with obesity was identified in Asian populations. This systematic Human Genome Epidemiology (HuGE) review showed convincingly that the SNPs rs6232, rs6234, and rs6235 in PCSK1 are associated with obesity in Caucasians.

  • 210. Stitziel, Nathan O.
    et al.
    Stirrups, Kathleen E.
    Masca, Nicholas G. D.
    Erdmann, Jeanette
    Ferrario, Paola G.
    Koenig, Inke R.
    Weeke, Peter E.
    Webb, Thomas R.
    Auer, Paul L.
    Schick, Ursula M.
    Lu, Yingchang
    Zhang, He
    Dube, Marie-Pierre
    Goel, Anuj
    Farrall, Martin
    Peloso, Gina M.
    Won, Hong-Hee
    Do, Ron
    van Iperen, Erik
    Kanoni, Stavroula
    Kruppa, Jochen
    Mahajan, Anubha
    Scott, Robert A.
    Willenborg, Christina
    Braund, Peter S.
    van Capelleveen, Julian C.
    Doney, Alex S. F.
    Donnelly, Louise A.
    Asselta, Rosanna
    Merlini, Piera A.
    Duga, Stefano
    Marziliano, Nicola
    Denny, Josh C.
    Shaffer, Christian M.
    El-Mokhtari, Nour Eddine
    Franke, Andre
    Gottesman, Omri
    Heilmann, Stefanie
    Hengstenberg, Christian
    Hoffmann, Per
    Holmen, Oddgeir L.
    Hveem, Kristian
    Jansson, Jan-Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Joeckel, Karl-Heinz
    Kessler, Thorsten
    Kriebel, Jennifer
    Laugwitz, Karl L.
    Marouli, Eirini
    Martinelli, Nicola
    McCarthy, Mark I.
    Van Zuydam, Natalie R.
    Meisinger, Christa
    Esko, Tonu
    Mihailov, Evelin
    Andersson Escher, Stefan
    Alver, Maris
    Moebus, Susanne
    Morris, Andrew D.
    Mueller-Nurasyid, Martina
    Nikpay, Majid
    Olivieri, Oliviero
    Perreault, Louis-Philippe Lemieux
    AlQarawi, Alaa
    Robertson, Neil R.
    Akinsanya, Karen O.
    Reilly, Dermot F.
    Vogt, Thomas F.
    Yin, Wu
    Asselbergs, Folkert W.
    Kooperberg, Charles
    Jackson, Rebecca D.
    Stahl, Eli
    Strauch, Konstantin
    Varga, Tibor V.
    Waldenberger, Melanie
    Zeng, Lingyao
    Kraja, Aldi T.
    Liu, Chunyu
    Ehret, Georg B.
    Newton-Cheh, Christopher
    Chasman, Daniel I.
    Chowdhury, Rajiv
    Ferrario, Marco
    Ford, Ian
    Jukema, J. Wouter
    Kee, Frank
    Kuulasmaa, Kari
    Nordestgaard, Borge G.
    Perola, Markus
    Saleheen, Danish
    Sattar, Naveed
    Surendran, Praveen
    Tregouet, David
    Young, Robin
    Howson, Joanna M. M.
    Butterworth, Adam S.
    Danesh, John
    Ardissino, Diego
    Bottinger, Erwin P.
    Erbel, Raimund
    Franks, Paul W.
    Harvard University; Umeå University Hospital; Lund University.
    Girelli, Domenico
    Hall, Alistair S.
    Hovingh, G. Kees
    Kastrati, Adnan
    Lieb, Wolfgang
    Meitinger, Thomas
    Kraus, William E.
    Shah, Svati H.
    McPherson, Ruth
    Orho-Melander, Marju
    Melander, Olle
    Metspalu, Andres
    Palmer, Colin N. A.
    Peters, Annette
    Rader, Daniel J.
    Reilly, Muredach P.
    Loos, Ruth J. F.
    Reiner, Alex P.
    Roden, Dan M.
    Tardif, Jean-Claude
    Thompson, John R.
    Wareham, Nicholas J.
    Watkins, Hugh
    Willer, Cristen J.
    Kathiresan, Sekar
    Deloukas, Panos
    Samani, Nilesh J.
    Schunkert, Heribert
    Coding Variation in ANGPTL4, LPL, and SVEP1 and the Risk of Coronary Disease2016Ingår i: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 374, nr 12, s. 1134-1144Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND The discovery of low-frequency coding variants affecting the risk of coronary artery disease has facilitated the identification of therapeutic targets. METHODS Through DNA genotyping, we tested 54,003 coding-sequence variants covering 13,715 human genes in up to 72,868 patients with coronary artery disease and 120,770 controls who did not have coronary artery disease. Through DNA sequencing, we studied the effects of loss-of-function mutations in selected genes. RESULTS We confirmed previously observed significant associations between coronary artery disease and low-frequency missense variants in the genes LPA and PCSK9. We also found significant associations between coronary artery disease and low-frequency missense variants in the genes SVEP1 (p.D2702G; minor-allele frequency, 3.60%; odds ratio for disease, 1.14; P = 4.2x10(-10)) and ANGPTL4 (p.E40K; minor-allele frequency, 2.01%; odds ratio, 0.86; P = 4.0x10(-8)), which encodes angiopoietin-like 4. Through sequencing of ANGPTL4, we identified 9 carriers of loss-of-function mutations among 6924 patients with myocardial infarction, as compared with 19 carriers among 6834 controls (odds ratio, 0.47; P = 0.04); carriers of ANGPTL4 loss-of-function alleles had triglyceride levels that were 35% lower than the levels among persons who did not carry a loss-of-function allele (P = 0.003). ANGPTL4 inhibits lipoprotein lipase; we therefore searched for mutations in LPL and identified a loss-of-function variant that was associated with an increased risk of coronary artery disease (p.D36N; minor-allele frequency, 1.9%; odds ratio, 1.13; P = 2.0x10(-4)) and a gain-of-function variant that was associated with protection from coronary artery disease (p.S447*; minor-allele frequency, 9.9%; odds ratio, 0.94; P = 2.5x10(-7)). CONCLUSIONS We found that carriers of loss-of-function mutations in ANGPTL4 had triglyceride levels that were lower than those among noncarriers; these mutations were also associated with protection from coronary artery disease.

  • 211. Sullivan, Shannon D.
    et al.
    Jablonski, Kathleen A.
    Florez, Jose C.
    Dabelea, Dana
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Dagogo-Jack, Sam
    Kim, Catherine
    Knowler, William C.
    Christophi, Costas A.
    Ratner, Robert
    Genetic Risk of Progression to Type 2 Diabetes and Response to Intensive Lifestyle or Metformin in Prediabetic Women With and Without a History of Gestational Diabetes Mellitus2014Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 37, nr 4, s. 909-911Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE The Diabetes Prevention Program (DPP) trial investigated rates of progression to diabetes among adults with prediabetes randomized to treatment with placebo, metformin, or intensive lifestyle intervention. Among women in the DPP, diabetes risk reduction with metformin was greater in women with prior gestational diabetes mellitus (GDM) compared with women without GDM but with one or more previous live births. RESEARCH DESIGN AND METHODS We asked if genetic variability could account for these differences by comparing beta-cell function and genetic risk scores (GRS), calculated from 34 diabetes-associated loci, between women with and without histories of GDM. RESULTS beta-Cell function was reduced in women with GDM. The GRS was positively associated with a history of GDM; however, the GRS did not predict progression to diabetes or modulate response to intervention. CONCLUSIONS These data suggest that a diabetes-associated GRS is associated with development of GDM and may characterize women at risk for development of diabetes due to beta-cell dysfunction.

  • 212. Sung, Yun J.
    et al.
    Winkler, Thomas W.
    de las Fuentes, Lisa
    Bentley, Amy R.
    Brown, Michael R.
    Kraja, Aldi T.
    Schwander, Karen
    Ntalla, Ioanna
    Guo, Xiuqing
    Franceschini, Nora
    Lu, Yingchang
    Cheng, Ching-Yu
    Sim, Xueling
    Vojinovic, Dina
    Marten, Jonathan
    Musani, Solomon K.
    Li, Changwei
    Feitosa, Mary F.
    Kilpelainen, Tuomas O.
    Richard, Melissa A.
    Noordam, Raymond
    Aslibekyan, Stella
    Aschard, Hugues
    Bartz, Traci M.
    Dorajoo, Rajkumar
    Liu, Yongmei
    Manning, Alisa K.
    Rankinen, Tuomo
    Smith, Albert Vernon
    Tajuddin, Salman M.
    Tayo, Bamidele O.
    Warren, Helen R.
    Zhao, Wei
    Zhou, Yanhua
    Matoba, Nana
    Sofer, Tamar
    Alver, Maris
    Amini, Marzyeh
    Boissel, Mathilde
    Chai, Jin Fang
    Chen, Xu
    Divers, Jasmin
    Gandin, Ilaria
    Gao, Chuan
    Giulianini, Franco
    Goel, Anuj
    Harris, Sarah E.
    Hartwig, Fernando Pires
    Horimoto, Andrea R. V. R.
    Hsu, Fang-Chi
    Jackson, Anne U.
    Kahonen, Mika
    Kasturiratne, Anuradhani
    Kuhnel, Brigitte
    Leander, Karin
    Lee, Wen-Jane
    Lin, Keng-Hung
    Luan, Jian' an
    McKenzie, Colin A.
    Meian, He
    Nelson, Christopher P.
    Rauramaa, Rainer
    Schupf, Nicole
    Scott, Robert A.
    Sheu, Wayne H. H.
    Stancakova, Alena
    Takeuchi, Fumihiko
    van der Most, Peter J.
    Varga, Tibor V.
    Wang, Heming
    Wang, Yajuan
    Ware, Erin B.
    Weiss, Stefan
    Wen, Wanqing
    Yanek, Lisa R.
    Zhang, Weihua
    Zhao, Jing Hua
    Afaq, Saima
    Alfred, Tamuno
    Amin, Najaf
    Arking, Dan
    Aung, Tin
    Barr, R. Graham
    Bielak, Lawrence F.
    Boerwinkle, Eric
    Bottinger, Erwin P.
    Braund, Peter S.
    Brody, Jennifer A.
    Broeckel, Ulrich
    Cabrera, Claudia P.
    Cade, Brian
    Caizheng, Yu
    Campbell, Archie
    Canouil, Mickael
    Chakravarti, Aravinda
    Chauhan, Ganesh
    Christensen, Kaare
    Cocca, Massimiliano
    Collins, Francis S.
    Connell, John M.
    de Mutsert, Renee
    de Silva, H. Janaka
    Debette, Stephanie
    Dorr, Marcus
    Duan, Qing
    Eaton, Charles B.
    Ehret, Georg
    Evangelou, Evangelos
    Faul, Jessica D.
    Fisher, Virginia A.
    Forouhi, Nita G.
    Franco, Oscar H.
    Friedlander, Yechiel
    Gao, He
    Gigante, Bruna
    Graff, Misa
    Gu, C. Charles
    Gu, Dongfeng
    Gupta, Preeti
    Hagenaars, Saskia P.
    Harris, Tamara B.
    He, Jiang
    Heikkinen, Sami
    Heng, Chew-Kiat
    Hirata, Makoto
    Hofman, Albert
    Howard, Barbara V.
    Hunt, Steven
    Irvin, Marguerite R.
    Jia, Yucheng
    Joehanes, Roby
    Justice, Anne E.
    Katsuya, Tomohiro
    Kaufman, Joel
    Kerrison, Nicola D.
    Khor, Chiea Chuen
    Koh, Woon-Puay
    Koistinen, Heikki A.
    Komulainen, Pirjo
    Kooperberg, Charles
    Krieger, Jose E.
    Kubo, Michiaki
    Kuusisto, Johanna
    Langefeld, Carl D.
    Langenberg, Claudia
    Launer, Lenore J.
    Lehne, Benjamin
    Lewis, Cora E.
    Li, Yize
    Lim, Sing Hui
    Lin, Shiow
    Liu, Ching-Ti
    Liu, Jianjun
    Liu, Jingmin
    Liu, Kiang
    Liu, Yeheng
    Loh, Marie
    Lohman, Kurt K.
    Long, Jirong
    Louie, Tin
    Magi, Reedik
    Mahajan, Anubha
    Meitinger, Thomas
    Metspalu, Andres
    Milani, Lili
    Momozawa, Yukihide
    Morris, Andrew P.
    Mosley, Thomas H., Jr.
    Munson, Peter
    Murray, Alison D.
    Nalls, Mike A.
    Nasri, Ubaydah
    Norris, Jill M.
    North, Kari
    Ogunniyi, Adesola
    Padmanabhan, Sandosh
    Palmas, Walter R.
    Palmer, Nicholette D.
    Pankow, James S.
    Pedersen, Nancy L.
    Peters, Annette
    Peyser, Patricia A.
    Polasek, Ozren
    Raitakari, Olli T.
    Renström, Frida
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Rice, Treva K.
    Ridker, Paul M.
    Robino, Antonietta
    Robinson, Jennifer G.
    Rose, Lynda M.
    Rudan, Igor
    Sabanayagam, Charumathi
    Salako, Babatunde L.
    Sandow, Kevin
    Schmidt, Carsten O.
    Schreiner, Pamela J.
    Scott, William R.
    Seshadri, Sudha
    Sever, Peter
    Sitlani, Colleen M.
    Smith, Jennifer A.
    Snieder, Harold
    Starr, John M.
    Strauch, Konstantin
    Tang, Hua
    Taylor, Kent D.
    Teo, Yik Ying
    Tham, Yih Chung
    Ultterlinden, Andre G.
    Waldenberger, Melanie
    Wang, Lihua
    Wang, Ya X.
    Bin Wei, Wen
    Williams, Christine
    Wilson, Gregory
    Wojczynski, Mary K.
    Yao, Jie
    Yuan, Jian-Min
    Zonderman, Alan B.
    Becker, Diane M.
    Boehnke, Michael
    Bowden, Donald W.
    Chambers, John C.
    Chen, Yii-Der Ida
    de Faire, Ulf
    Deary, Ian J.
    Esko, Tonu
    Farrall, Martin
    Forrester, Terrence
    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; Harvard T.H. Chan School of Public Health, Department of Nutrition, Harvard University, Boston, MA, USA.
    Freedman, Barry I.
    Froguel, Philippe
    Gasparini, Paolo
    Gieger, Christian
    Horta, Bernardo Lessa
    Hung, Yi-Jen
    Jonas, Jost B.
    Kato, Norihiro
    Kooner, Jaspal S.
    Laakso, Markku
    Lehtimaki, Terho
    Liang, Kae-Woei
    Magnusson, Patrik K. E.
    Newman, Anne B.
    Oldehinkel, Albertine J.
    Pereira, Alexandre C.
    Redline, Susan
    Rettig, Rainer
    Samani, Nilesh J.
    Scott, James
    Shu, Xiao-Ou
    van der Harst, Pim
    Wagenknecht, Lynne E.
    Wareham, Nicholas J.
    Watkins, Hugh
    Weir, David R.
    Wickremasinghe, Ananda R.
    Wu, Tangchun
    Zheng, Wei
    Kamatani, Yoichiro
    Laurie, Cathy C.
    Bouchard, Claude
    Cooper, Richard S.
    Evans, Michele K.
    Gudnason, Vilmundur
    Kardia, Sharon L. R.
    Kritchevsky, Stephen B.
    Levy, Daniel
    O'Connell, Jeff R.
    Psaty, Bruce M.
    van Dam, Rob M.
    Sims, Mario
    Arnett, Donna K.
    Mook-Kanamori, Dennis O.
    Kelly, Tanika N.
    Fox, Ervin R.
    Hayward, Caroline
    Fornage, Myriam
    Rotimi, Charles N.
    Province, Michael A.
    van Duijn, Cornelia M.
    Tai, E. Shyong
    Wong, Tien Yin
    Loos, Ruth J. F.
    Reiner, Alex P.
    Rotter, Jerome I.
    Zhu, Xiaofeng
    Bierut, Laura J.
    Gauderman, W. James
    Caulfield, Mark J.
    Elliott, Paul
    Rice, Kenneth
    Munroe, Patricia B.
    Morrison, Alanna C.
    Cupples, L. Adrienne
    Rao, Dabeeru C.
    Chasman, Daniel I.
    A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure2018Ingår i: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 102, nr 3, s. 375-400Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals. Stage 1 analysis examined similar to 18.8 million SNPs and small insertion/deletion variants in 129,913 individuals from four ancestries (European, African, Asian, and Hispanic) with follow-up analysis of promising variants in 480,178 additional individuals from five ancestries. We identified 15 loci that were genome-wide significant (p < 5 x 10(-8)) in stage 1 and formally replicated in stage 2. A combined stage 1 and 2 meta-analysis identified 66 additional genome-wide significant loci (13, 35, and 18 loci in European, African, and trans-ancestry, respectively). A total of 56 known BP loci were also identified by our results (p < 5 x 10(-8)). Of the newly identified loci, ten showed significant interaction with smoking status, but none of them were replicated in stage 2. Several loci were identified in African ancestry, highlighting the importance of genetic studies in diverse populations. The identified loci show strong evidence for regulatory features and support shared pathophysiology with cardiometabolic and addiction traits. They also highlight a role in BP regulation for biological candidates such as modulators of vascular structure and function (CDKN1B, BCAR1-CFDP1, PXDN, EEA1), ciliopathies (SDCCAG8, RPGRIP1L), telomere maintenance (TNKS, PINX1, AKTIP), and central dopaminergic signaling MSRA, EBF2).

  • 213. Surendran, Praveen
    et al.
    Drenos, Fotios
    Young, Robin
    Warren, Helen
    Cook, James P.
    Manning, Alisa K.
    Grarup, Niels
    Sim, Xueling
    Barnes, Daniel R.
    Witkowska, Kate
    Staley, James R.
    Tragante, Vinicius
    Tukiainen, Taru
    Yaghootkar, Hanieh
    Masca, Nicholas
    Freitag, Daniel F.
    Ferreira, Teresa
    Giannakopoulou, Olga
    Tinker, Andrew
    Harakalova, Magdalena
    Mihailov, Evelin
    Liu, Chunyu
    Kraja, Aldi T.
    Nielsen, Sune Fallgaard
    Rasheed, Asif
    Samue, Maria
    Zhao, Wei
    Bonnycastle, Lori L.
    Jackson, Anne U.
    Narisu, Narisu
    Swift, Amy J.
    Southam, Lorraine
    Marten, Jonathan
    Huyghe, Jeroen R.
    Stancakova, Alena
    Fava, Cristiano
    Ohlsson, Therese
    Matchan, Angela
    Stirrups, Kathleen E.
    Bork-Jensen, Jette
    Gjesing, Anette P.
    Kontto, Jukka
    Perola, Markus
    Shaw-Hawkins, Susan
    Havulinna, Aki S.
    Zhang, He
    Donnelly, Louise A.
    Groves, Christopher J.
    Rayner, N. William
    Neville, Matt J.
    Robertson, Neil R.
    Yiorkas, Andrianos M.
    Herzig, Karl-Heinz
    Kajantie, Eero
    Zhang, Weihua
    Willems, Sara M.
    Lannfelt, Lars
    Malerba, Giovanni
    Soranzo, Nicole
    Trabetti, Elisabetta
    Verweij, Niek
    Evangelou, Evangelos
    Moayyeri, Alireza
    Vergnaud, Anne-Claire
    Nelson, Christopher P.
    Poveda, Alaitz
    Varga, Tibor V.
    Caslake, Muriel
    de Craen, Anton J. M.
    Trompet, Stella
    Luan, Jian'an
    Scott, Robert A.
    Harris, Sarah E.
    Liewald, David C. M.
    Marioni, Riccardo
    Menni, Cristina
    Farmaki, Aliki-Eleni
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Renström, Frida
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden.
    Huffman, Jennifer E.
    Hassinen, Maija
    Burgess, Stephen
    Vasan, Ramachandran S.
    Felix, Janine F.
    Uria-Nickelsen, Maria
    Malarstign, Anders
    Reilly, Dermot F.
    Hoek, Maarten
    Vogt, Thomas F.
    Lin, Honghuang
    Lieb, Wolfgang
    Traylor, Matthew
    Markus, Hugh S.
    Highland, Heather M.
    Justice, Anne E.
    Marouli, Eirini
    Lindstrom, Jaana
    Uusitupa, Matti
    Komulainen, Pirjo
    Lakka, Timo A.
    Rauramaa, Rainer
    Polasek, Ozren
    Rudan, Igor
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    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, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA.
    Dedoussis, George
    Spector, Timothy D.
    Jousilahti, Pekka
    Mannisto, Satu
    Deary, Ian J.
    Starr, John M.
    Langenberg, Claudia
    Wareham, Nick J.
    Brown, Morris J.
    Dominiczak, Anna F.
    Connell, John M.
    Jukema, J. Wouter
    Sattar, Naveed
    Ford, Ian
    Packard, Chris J.
    Esko, Tonu
    Magi, Reedik
    Metspalu, Andres
    de Boer, Rudolf A.
    van der Meer, Peter
    van der Harst, Pim
    Gambaro, Giovanni
    Ingelsson, Erik
    Lind, Lars
    de Bakker, Paul I. W.
    Numans, Mattijs E.
    Brandslund, Ivan
    Christensen, Cramer
    Petersen, Eva R. B.
    Korpi-Hyovalti, Eeva
    Oksa, Heikki
    Chambers, John C.
    Kooner, Jaspal S.
    Blakemore, Alexandra I. F.
    Franks, Steve
    Jarvelin, Marjo-Riitta
    Husemoen, Lise L.
    Linneberg, Allan
    Skaaby, Tea
    Thuesen, Betina
    Karpe, Fredrik
    Tuomilehto, Jaakko
    Doney, Alex S. F.
    Morris, Andrew D.
    Palmer, Colin N. A.
    Holmen, Oddgeir Lingaas
    Hveem, Kristian
    Willer, Cristen J.
    Tuomi, Tiinamaija
    Groop, Leif
    Karajamaki, AnneMari
    Palotie, Aarno
    Ripatti, Samuli
    Salomaa, Veikko
    Alam, Dewan S.
    Majmnder, Abdulla Al Shafi
    Di Angelantonio, Emanuele
    Chowdhury, Rajiv
    McCarthy, Mark I.
    Poulter, Neil
    Stanton, Alice V.
    Sever, Peter
    Amouyel, Philippe
    Arveiler, Dominique
    Blankenberg, Stefan
    Ferrieres, Jean
    Kee, Frank
    Kuulasmaa, Kari
    Muller-Nurasyid, Martina
    Veronesi, Giovanni
    Virtamo, Jarmo
    Deloukas, Panos
    Elliott, Paul
    Zeggini, Eleftheria
    Kathiresan, Sekar
    Melander, Olle
    Kuusisto, Johanna
    Laakso, Markku
    Padmanabhan, Sandosh
    Porteous, David J.
    Hayward, Caroline
    Scotland, Generation
    Collins, Francis S.
    Mohlke, Karen L.
    Hansen, Torben
    Pedersen, Oluf
    Boehnke, Michael
    Stringham, Heather M.
    Frossard, Philippe
    Newton-Cheh, Christopher
    Tobin, Martin D.
    Nordestgaard, Borge Gronne
    Caulfield, Mark J.
    Mahajan, Anubha
    Morris, Andrew P.
    Tomaszewski, Maciej
    Samani, Nilesh J.
    Saleheen, Danish
    Asselbergs, Folkert W.
    Lindgren, Cecilia M.
    Danesh, John
    Wain, Louise V.
    Butterworth, Adam S.
    Howson, Joanna M. M.
    Munroe, Patricia B.
    Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension2016Ingår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 48, nr 10, s. 1151-1161Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low frequency and common genetic variants in up to 192,763 individuals and used similar to 155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.

  • 214. Tanaka, Toshiko
    et al.
    Ngwa, Julius S.
    van Rooij, Frank J. A.
    Zillikens, M. Carola
    Wojczynski, Mary K.
    Frazier-Wood, Alexis C.
    Houston, Denise K.
    Kanoni, Stavroula
    Lemaitre, Rozenn N.
    Luan, Jian'an
    Mikkila, Vera
    Renstrom, Frida
    Sonestedt, Emily
    Zhao, Jing Hua
    Chu, Audrey Y.
    Qi, Lu
    Chasman, Daniel I.
    Otto, Marcia C. de Oliveira
    Dhurandhar, Emily J.
    Feitosa, Mary F.
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Khaw, Kay-Tee
    Lohman, Kurt K.
    Manichaikul, Ani
    McKeown, Nicola M.
    Mozaffarian, Dariush
    Singleton, Andrew
    Stirrups, Kathleen
    Viikari, Jorma
    Ye, Zheng
    Bandinelli, Stefania
    Barroso, Ines
    Deloukas, Panos
    Forouhi, Nita G.
    Hofman, Albert
    Liu, Yongmei
    Lyytikainen, Leo-Pekka
    North, Kari E.
    Dimitriou, Maria
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Kahonen, Mika
    Langenberg, Claudia
    Ordovas, Jose M.
    Uitterlinden, Andre G.
    Hu, Frank B.
    Kalafati, Ioanna-Panagiota
    Raitakari, Olli
    Franco, Oscar H.
    Johnson, Andrew
    Emilsson, Valur
    Schrack, Jennifer A.
    Semba, Richard D.
    Siscovick, David S.
    Arnett, Donna K.
    Borecki, Ingrid B.
    Franks, Paul
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Kritchevsky, Stephen B.
    Lehtimaki, Terho
    Loos, Ruth J. F.
    Orho-Melander, Marju
    Rotter, Jerome I.
    Wareham, Nicholas J.
    Witteman, Jacqueline C. M.
    Ferrucci, Luigi
    Dedoussis, George
    Cupples, L. Adrienne
    Nettleton, Jennifer A.
    Genome-wide meta-analysis of observational studies shows common genetic variants associated with macronutrient intake2013Ingår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 97, nr 6, s. 1395-1402Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Macronutrient intake varies substantially between individuals, and there is evidence that this variation is partly accounted for by genetic variants.

    Objective: The objective of the study was to identify common genetic variants that are associated with macronutrient intake.

    Design: We performed 2-stage genome-wide association (GWA) meta-analysis of macronutrient intake in populations of European descent. Macronutrients were assessed by using food-frequency questionnaires and analyzed as percentages of total energy consumption from total fat, protein, and carbohydrate. From the discovery GWA (n = 38,360), 35 independent loci associated with macronutrient intake at P < 5 x 10(-6) were identified and taken forward to replication in 3 additional cohorts (n = 33,533) from the DietGen Consortium. For one locus, fat mass obesity-associated protein (FTO), cohorts with Illumina MetaboChip genotype data (n 7724) provided additional replication data.

    Results: A variant in the chromosome 19 locus (rs838145) was associated with higher carbohydrate (beta +/- SE: 0.25 +/- 0.04%; P = 1.68 x 10(-8)) and lower fat (beta = SE: -0.21 +/- 0.04%; P = 1.57 x 10(-9)) consumption. A candidate gene in this region, fibroblast growth factor 21 (FGF21), encodes a fibroblast growth factor involved in glucose and lipid metabolism. The variants in this locus were associated with circulating FGF21 protein concentrations (P < 0.05) but not mRNA concentrations in blood or brain. The body mass index (BMI) increasing allele of the FTO variant (rs1421085) was associated with higher protein intake (beta +/- SE: 0.10 +/- 0.02%; P = 9.96 x 10(-10)), independent of BMI (after adjustment for BMI, beta +/- SE: 0.08 +/- 0.02%; P = 3.15 x 10(-7)).

    Conclusion: Our results indicate that variants in genes involved in nutrient metabolism and obesity are associated with macronutrient consumption in humans. Trials related to this study were registered at clinicaltrials.gov as NCT00005131 (Atherosclerosis Risk in Communities), NCT00005133 (Cardiovascular Health Study), NCT00005136 (Family Heart Study), NCT00005121 (Framingham Heart Study), NCT00083369 (Genetic and Environmental Determinants of Triglycerides), NCT01331512 (InCHIANTI Study), and NCT00005487 (Multi-Ethnic Study of Atherosclerosis).

  • 215. Timpka, Simon
    et al.
    Fraser, Abigail
    Schyman, Tommy
    Stuart, Jennifer J.
    Asvold, Bjorn Olav
    Mogren, Ingrid
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    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 Malmö; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
    Rich-Edwards, Janet W.
    The value of pregnancy complication history for 10-year cardiovascular disease risk prediction in middle-aged women2018Ingår i: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 33, nr 10, s. 1003-1010Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Women with a history of hypertensive disorders of pregnancy (HDP; preeclampsia and gestational hypertension) or delivering low birth weight offspring (LBW; < 2500 g) have twice the risk of cardiovascular disease (CVD). We aimed to study the extent to which history of these pregnancy complications improves CVD risk prediction above and beyond conventional predictors. Parous women attended standardized clinical visits in Sweden. Data were linked to registries of deliveries and CVD. Participants were followed for a first CVD event within 10 years from age 50 (n = 7552) and/or 60 years (n = 5360) and the predictive value of each pregnancy complication above and beyond conventional predictors was investigated. History of LBW offspring was associated with increased risk of CVD when added to conventional predictors in women 50 years of age [Hazard ratio 1.68, 95% Confidence interval (CI) 1.19, 2.37] but not at age 60 (age interaction p = 0.04). However, at age 50 years CVD prediction was not further improved by information on LBW offspring, except that a greater proportion of the women who developed CVD were assigned to a higher risk category (categorical net reclassification improvement for events 0.038, 95% CI 0.003, 0.074). History of HDP was not associated with CVD when adjusted for reference model predictors. In conclusion, a history of pregnancy complications can identify women with increased risk of CVD midlife. However, considered with conventional risk factors, history of HDP or having delivered LBW offspring did not meaningfully improve 10-year CVD risk prediction in women age 50 years or older.

  • 216. Timpka, Simon
    et al.
    Markovitz, Amanda
    Schyman, Tommy
    Mogren, Ingrid
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    Fraser, Abigail
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Clinical Sciences Malmö, Lund University, Malmö, Sweden; Harvard T.H. Chan School of Public Health, Boston, MA, USA.
    Rich-Edwards, Janet W.
    Midlife development of type 2 diabetes and hypertension in women by history of hypertensive disorders of pregnancy2018Ingår i: Cardiovascular Diabetology, ISSN 1475-2840, E-ISSN 1475-2840, Vol. 17, artikel-id 124Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Women with history of hypertensive disorders of pregnancy (HDP) are at increased risk of early onset cardiovascular disease and type 2 diabetes (T2D). We aimed to investigate the extent to which HDP is also associated with midlife development of T2D and hypertension above and beyond established risk factors.

    Methods: We included parous women who attended population-based structured clinical visits at age 50 and 60 years in Sweden 1991-2013 (N = 6587). Women with prior diabetes mellitus, stroke, or ischemic heart disease at age 50 years were excluded. Data on reproductive history were collected from registries. To study the association between history of HDP and the between-visits development of T2D, hypertension, and clinical risk factors of cardio-metabolic disease (body mass index (BMI), blood pressure, and total cholesterol), we utilized multivariable adjusted regression models (logistic, log binomial, and linear regression, respectively). Models included data on outcome risk factors at age 50 years, e.g. BMI, 75 g 2 h oral glucose tolerance test result, and mean arterial pressure, respectively.

    Results: Between ages 50 and 60 years, 5.8% of initially disease-free women developed T2D and 31.6% developed hypertension. History of HDP was associated with increased risk of developing T2D between age 50 and 60 years even when adjusting for risk factors, including BMI, at age 50 years (odds ratio (OR) 1.96, 95% confidence interval (CI) 1.29-2.98). By contrast, the higher risk of developing hypertension observed in women with history of HDP (relative risk (RR) 1.47, 95% CI 1.22-1.78) was attenuated when adjusted for risk factors (RR 1.09, 95% CI 0.94-1.25). Participants with a history of HDP had higher mean BMI and blood pressure at age 50 years, with levels roughly corresponding to those observed at age 60 years in unaffected women.

    Conclusions: Women with history of HDP are not only at higher risk of cardiometabolic disease during their reproductive years, but HDP is also associated with midlife T2D development above and beyond established risk factors.

  • 217.
    Toss, Fredrik
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin.
    Wiklund, Peder
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin.
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Eriksson, Marie
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Gustafson, Yngve
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Nordström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Nordström, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin.
    Abdominal and gynoid adiposity and the risk of stroke2011Ingår i: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 35, nr 11, s. 1427-1432Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Previous studies have indicated that fat distribution is important in the development of cardiovascular disease (CVD). We investigated the association between fat distribution, as measured by dual energy X-ray absorptiometry (DXA), and the incidence of stroke.

    Methods: A cohort of 2751 men and women aged 40 years was recruited. Baseline levels of abdominal, gynoid and total body fat were measured by DXA. Body mass index (BMI, kg m(-2)) was calculated. Stroke incidence was recorded using the regional stroke registry until subjects reached 75 years of age.

    Results: During a mean follow-up time of 8 years and 9 months, 91 strokes occurred. Of the adiposity indices accessed abdominal fat mass was the best predictor of stroke in women (hazard ratio (HR)=1.66, 95% confidence interval (CI)=1.23-2.24 per standard deviation increase), whereas the ratio of gynoid fat to total fat mass was associated with a decreased risk of stroke (HR=0.72, 95% CI=0.54-0.96). Abdominal fat mass was the only of the adiposity indices assessed that was found to be a significant predictor of stroke in men (HR=1.49, 95% CI=1.06-2.09). The associations between abdominal fat mass and stroke remained significant in both women and men after adjustment for BMI (HR=1.80, 95% CI=1.06-3.07; HR=1.71, 95% CI=1.13-2.59, respectively). However, in a subgroup analyses abdominal fat was not a significant predictor after further adjustment for diabetes, smoking and hypertension.

    Conclusion: Abdominal fat mass is a risk factor for stroke independent of BMI, but not independent of diabetes, smoking and hypertension. This indicates that the excess in stroke risk associated with abdominal fat mass is at least partially mediated through traditional stroke risk factors.International Journal of Obesity advance online publication, 22 February 2011; doi:10.1038/ijo.2011.9.

  • 218. Turcot, Valerie
    et al.
    Lu, Yingchang
    Highland, Heather M.
    Schurmann, Claudia
    Justice, Anne E.
    Fine, Rebecca S.
    Bradfield, Jonathan P.
    Esko, Tonu
    Giri, Ayush
    Graff, Mariaelisa
    Guo, Xiuqing
    Hendricks, Audrey E.
    Karaderi, Tugce
    Lempradl, Adelheid
    Locke, Adam E.
    Mahajan, Anubha
    Marouli, Eirini
    Sivapalaratnam, Suthesh
    Young, Kristin L.
    Alfred, Tamuno
    Feitosa, Mary F.
    Masca, Nicholas G. D.
    Manning, Alisa K.
    Medina-Gomez, Carolina
    Mudgal, Poorva
    Ng, Maggie C. Y.
    Reiner, Alex P.
    Vedantam, Sailaja
    Willems, Sara M.
    Winkler, Thomas W.
    Abecasis, Goncalo
    Aben, Katja K.
    Alam, Dewan S.
    Alharthi, Sameer E.
    Allison, Matthew
    Amouyel, Philippe
    Asselbergs, Folkert W.
    Auer, Paul L.
    Balkau, Beverley
    Bang, Lia E.
    Barroso, Ines
    Bastarache, Lisa
    Benn, Marianne
    Bergmann, Sven
    Bielak, Lawrence F.
    Blueher, Matthias
    Boehnke, Michael
    Boeing, Heiner
    Boerwinkle, Eric
    Boeger, Carsten A.
    Bork-Jensen, Jette
    Bots, Michiel L.
    Bottinger, Erwin P.
    Bowden, Donald W.
    Brandslund, Ivan
    Breen, Gerome
    Brilliant, Murray H.
    Broer, Linda
    Brumat, Marco
    Burt, Amber A.
    Butterworth, Adam S.
    Campbell, Peter T.
    Cappellani, Stefania
    Carey, David J.
    Catamo, Eulalia
    Caulfield, Mark J.
    Chambers, John C.
    Chasman, Daniel I.
    Chen, Yii-Der I.
    Chowdhury, Rajiv
    Christensen, Cramer
    Chu, Audrey Y.
    Cocca, Massimiliano
    Collins, Francis S.
    Cook, James P.
    Corley, Janie
    Galbany, Jordi Corominas
    Cox, Amanda J.
    Crosslin, David S.
    Cuellar-Partida, Gabriel
    D'Eustacchio, Angela
    Danesh, John
    Davies, Gail
    Bakker, Paul I. W.
    Groot, Mark C. H.
    Mutsert, Renee
    Deary, Ian J.
    Dedoussis, George
    Demerath, Ellen W.
    Heijer, Martin
    Hollander, Anneke I.
    Ruijter, Hester M.
    Dennis, Joe G.
    Denny, Josh C.
    Angelantonio, Emanuele
    Drenos, Fotios
    Du, Mengmeng
    Dube, Marie-Pierre
    Dunning, Alison M.
    Easton, Douglas F.
    Edwards, Todd L.
    Ellinghaus, David
    Ellinor, Patrick T.
    Elliott, Paul
    Evangelou, Evangelos
    Farmaki, Aliki-Eleni
    Farooqi, I. Sadaf
    Faul, Jessica D.
    Fauser, Sascha
    Feng, Shuang
    Ferrannini, Ele
    Ferrieres, Jean
    Florez, Jose C.
    Ford, Ian
    Fornage, Myriam
    Franco, Oscar H.
    Franke, Andre
    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, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
    Friedrich, Nele
    Frikke-Schmidt, Ruth
    Galesloot, Tessel E.
    Gan, Wei
    Gandin, Ilaria
    Gasparini, Paolo
    Gibson, Jane
    Giedraitis, Vilmantas
    Gjesing, Anette P.
    Gordon-Larsen, Penny
    Gorski, Mathias
    Grabe, Hans-Joergen
    Grant, Struan F. A.
    Grarup, Niels
    Griffiths, Helen L.
    Grove, Megan L.
    Gudnason, Vilmundur
    Gustafsson, Stefan
    Haessler, Jeff
    Hakonarson, Hakon
    Hammerschlag, Anke R.
    Hansen, Torben
    Harris, Kathleen Mullan
    Harris, Tamara B.
    Hattersley, Andrew T.
    Have, Christian T.
    Hayward, Caroline
    He, Liang
    Heard-Costa, Nancy L.
    Heath, Andrew C.
    Heid, Iris M.
    Helgeland, Oyvind
    Hernesniemi, Jussi
    Hewitt, Alex W.
    Holmen, Oddgeir L.
    Hovingh, G. Kees
    Howson, Joanna M. M.
    Hu, Yao
    Huang, Paul L.
    Huffman, Jennifer E.
    Ikram, M. Arfan
    Ingelsson, Erik
    Jackson, Anne U.
    Jansson, Jan-Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Research Unit Skellefteå, Skellefteå, Sweden.
    Jarvik, Gail P.
    Jensen, Gorm B.
    Jia, Yucheng
    Johansson, Stefan
    Jorgensen, Marit E.
    Jorgensen, Torben
    Jukema, J. Wouter
    Kahali, Bratati
    Kahn, Rene S.
    Kahonen, Mika
    Kamstrup, Pia R.
    Kanoni, Stavroula
    Kaprio, Jaakko
    Karaleftheri, Maria
    Kardia, Sharon L. R.
    Karpe, Fredrik
    Kathiresan, Sekar
    Kee, Frank
    Kiemeney, Lambertus A.
    Kim, Eric
    Kitajima, Hidetoshi
    Komulainen, Pirjo
    Kooner, Jaspal S.
    Kooperberg, Charles
    Korhonen, Tellervo
    Kovacs, Peter
    Kuivaniemi, Helena
    Kutalik, Zoltan
    Kuulasmaa, Kari
    Kuusisto, Johanna
    Laakso, Markku
    Lakka, Timo A.
    Lamparter, David
    Lange, Ethan M.
    Lange, Leslie A.
    Langenberg, Claudia
    Larson, Eric B.
    Lee, Nanette R.
    Lehtimaki, Terho
    Lewis, Cora E.
    Li, Huaixing
    Li, Jin
    Li-Gao, Ruifang
    Lin, Honghuang
    Lin, Keng-Hung
    Lin, Li-An
    Lin, Xu
    Lind, Lars
    Lindstrom, Jaana
    Linneberg, Allan
    Liu, Ching-Ti
    Liu, Dajiang J.
    Liu, Yongmei
    Lo, Ken S.
    Lophatananon, Artitaya
    Lotery, Andrew J.
    Loukola, Anu
    Luan, Jian'an
    Lubitz, Steven A.
    Lyytikainen, Leo-Pekka
    Mannisto, Satu
    Marenne, Gaelle
    Mazul, Angela L.
    McCarthy, Mark I.
    McKean-Cowdin, Roberta
    Medland, Sarah E.
    Meidtner, Karina
    Milani, Lili
    Mistry, Vanisha
    Mitchell, Paul
    Mohlke, Karen L.
    Moilanen, Leena
    Moitry, Marie
    Montgomery, Grant W.
    Mook-Kanamori, Dennis O.
    Moore, Carmel
    Mori, Trevor A.
    Morris, Andrew D.
    Morris, Andrew P.
    Mueller-Nurasyid, Martina
    Munroe, Patricia B.
    Nalls, Mike A.
    Narisu, Narisu
    Nelson, Christopher P.
    Neville, Matt
    Nielsen, Sune F.
    Nikus, Kjell
    Njolstad, Pal R.
    Nordestgaard, Borge G.
    Nyholt, Dale R.
    O'Connel, Jeffrey R.
    O'Donoghue, Michelle L.
    Loohuis, Loes M. Olde
    Ophoff, Roel A.
    Owen, Katharine R.
    Packard, Chris J.
    Padmanabhan, Sandosh
    Palmer, Colin N. A.
    Palmer, Nicholette D.
    Pasterkamp, Gerard
    Patel, Aniruddh P.
    Pattie, Alison
    Pedersen, Oluf
    Peissig, Peggy L.
    Peloso, Gina M.
    Pennell, Craig E.
    Perola, Markus
    Perry, James A.
    Perry, John R. B.
    Pers, Tune H.
    Person, Thomas N.
    Peters, Annette
    Petersen, Eva R. B.
    Peyser, Patricia A.
    Pirie, Ailith
    Polasek, Ozren
    Polderman, Tinca J.
    Puolijoki, Hannu
    Raitakari, Olli T.
    Rasheed, Asif
    Rauramaa, Rainer
    Reilly, Dermot F.
    Renström, Frida
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden.
    Rheinberger, Myriam
    Ridker, Paul M.
    Rioux, John D.
    Rivas, Manuel A.
    Roberts, David J.
    Robertson, Neil R.
    Robino, Antonietta
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Rudan, Igor
    Ruth, Katherine S.
    Saleheen, Danish
    Salomaa, Veikko
    Samani, Nilesh J.
    Sapkota, Yadav
    Sattar, Naveed
    Schoen, Robert E.
    Schreiner, Pamela J.
    Schulze, Matthias B.
    Scott, Robert A.
    Segura-Lepe, Marcelo P.
    Shah, Svati H.
    Sheu, Wayne H. -H.
    Sim, Xueling
    Slater, Andrew J.
    Small, Kerrin S.
    Smith, Albert V.
    Southam, Lorraine
    Spector, Timothy D.
    Speliotes, Elizabeth K.
    Starr, John M.
    Stefansson, Kari
    Steinthorsdottir, Valgerdur
    Stirrups, Kathleen E.
    Strauch, Konstantin
    Stringham, Heather M.
    Stumvoll, Michael
    Sun, Liang
    Surendran, Praveen
    Swift, Amy J.
    Tada, Hayato
    Tansey, Katherine E.
    Tardif, Jean-Claude
    Taylor, Kent D.
    Teumer, Alexander
    Thompson, Deborah J.
    Thorleifsson, Gudmar
    Thorsteinsdottir, Unnur
    Thuesen, Betina H.
    Toenjes, Anke
    Tromp, Gerard
    Trompet, Stella
    Tsafantakis, Emmanouil
    Tuomilehto, Jaakko
    Tybjaerg-Hansen, Anne
    Tyrer, Jonathan P.
    Uher, Rudolf
    Uitterlinden, Andre G.
    Uusitupa, Matti
    Laan, Sander W.
    Duijn, Cornelia M.
    Leeuwen, Nienke
    van Setten, Jessica
    Vanhala, Mauno
    Varbo, Anette
    Varga, Tibor V.
    Varma, Rohit
    Edwards, Digna R. Velez
    Vermeulen, Sita H.
    Veronesi, Giovanni
    Vestergaard, Henrik
    Vitart, Veronique
    Vogt, Thomas F.
    Voelker, Uwe
    Vuckovic, Dragana
    Wagenknecht, Lynne E.
    Walker, Mark
    Wallentin, Lars
    Wang, Feijie
    Wang, Carol A.
    Wang, Shuai
    Wang, Yiqin
    Ware, Erin B.
    Wareham, Nicholas J.
    Warren, Helen R.
    Waterworth, Dawn M.
    Wessel, Jennifer
    White, Harvey D.
    Willer, Cristen J.
    Wilson, James G.
    Witte, Daniel R.
    Wood, Andrew R.
    Wu, Ying
    Yaghootkar, Hanieh
    Yao, Jie
    Yao, Pang
    Yerges-Armstrong, Laura M.
    Young, Robin
    Zeggini, Eleftheria
    Zhan, Xiaowei
    Zhang, Weihua
    Zhao, Jing Hua
    Zhao, Wei
    Zhou, Wei
    Zondervan, Krina T.
    Rotter, Jerome I.
    Pospisilik, John A.
    Rivadeneira, Fernando
    Borecki, Ingrid B.
    Deloukas, Panos
    Frayling, Timothy M.
    Lettre, Guillaume
    North, Kari E.
    Lindgren, Cecilia M.
    Hirschhorn, Joel N.
    Loos, Ruth J. F.
    Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity2018Ingår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 50, nr 1, s. 26-41Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.

  • 219. van Hees, Vincent
    et al.
    Renström, Frida
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Wright, A
    Gradmark, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Catt, M
    Chen, K
    Löf, M
    Bluck, L
    Wareham, NJ
    Ekelund, U
    Brage, S
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Estimation of daily energy expenditure in pregnant and non-pregnant women using a wrist-worn tri-axial accelerometer2011Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, nr 7, s. e22922-Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background Few studies have compared the validity of objective measures of physical activity energy expenditure (PAEE) in pregnant and non-pregnant women.  PAEE is commonly estimated with accelerometers attached to the hip or waist, but little is known about the validity and participant acceptability of wrist attachment. The objective of the current study was to assess the validity of a simple summary measure derived from a wrist-worn accelerometer (GENEA, Unilever Discover, UK) to estimate PAEE in pregnant and non-pregnant women, and to evaluate participant acceptability.

     

    Methods  Non-pregnant (N=73) and pregnant (N=35) Swedish women (aged 20–35 yrs) wore the accelerometer on their wrist for 10 days during which total energy expenditure (TEE) was assessed using doubly-labelled water. PAEE was calculated as 0.9 x TEE - REE. British participants (N=99; aged 22–65 yrs) wore accelerometers on their non-dominant wrist and hip for seven days and were asked to score the acceptability of monitor placement (scored 1 [least] through 10 [most] acceptable).

     

    Results There was no significant correlation between body weight and PAEE. In non-pregnant women, acceleration explained 24% of the variation in PAEE, which decreased to 17% in leave-one-out cross-validation. In pregnant women, acceleration explained 11% of the variation in PAEE, which was not significant in leave-one-out cross-validation. Median (IQR) acceptability of wrist and hip placement was 9(8-10) and 9(7-10), respectively; a within-individual difference of 0.47 was significant (p<.001).

     

    Conclusions A simple summary measure derived from a wrist-worn tri-axial accelerometer adds significantly to the prediction of energy expenditure in non-pregnant women and is scored acceptable by participants.

  • 220. van Hees, Vincent T.
    et al.
    Gorzelniak, Lukas
    Leon, Emmanuel Carlos Dean
    Eder, Martin
    Pias, Marcelo
    Taherian, Salman
    Ekelund, Ulf
    Renström, Frida
    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.
    Horsch, Alexander
    Brage, Soren
    Separating Movement and Gravity Components in an Acceleration Signal and Implications for the Assessment of Human Daily Physical Activity2013Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 4, s. e61691-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Human body acceleration is often used as an indicator of daily physical activity in epidemiological research. Raw acceleration signals contain three basic components: movement, gravity, and noise. Separation of these becomes increasingly difficult during rotational movements. We aimed to evaluate five different methods (metrics) of processing acceleration signals on their ability to remove the gravitational component of acceleration during standardised mechanical movements and the implications for human daily physical activity assessment. Methods: An industrial robot rotated accelerometers in the vertical plane. Radius, frequency, and angular range of motion were systematically varied. Three metrics (Euclidian norm minus one [ENMO], Euclidian norm of the high-pass filtered signals [HFEN], and HFEN plus Euclidean norm of low-pass filtered signals minus 1 g [HFEN+]) were derived for each experimental condition and compared against the reference acceleration (forward kinematics) of the robot arm. We then compared metrics derived from human acceleration signals from the wrist and hip in 97 adults (22-65 yr), and wrist in 63 women (20-35 yr) in whom daily activity-related energy expenditure (PAEE) was available. Results: In the robot experiment, HFEN+ had lowest error during (vertical plane) rotations at an oscillating frequency higher than the filter cut-off frequency while for lower frequencies ENMO performed better. In the human experiments, metrics HFEN and ENMO on hip were most discrepant (within- and between-individual explained variance of 0.90 and 0.46, respectively). ENMO, HFEN and HFEN+ explained 34%, 30% and 36% of the variance in daily PAEE, respectively, compared to 26% for a metric which did not attempt to remove the gravitational component (metric EN). Conclusion: In conclusion, none of the metrics as evaluated systematically outperformed all other metrics across a wide range of standardised kinematic conditions. However, choice of metric explains different degrees of variance in daily human physical activity.

  • 221. Varga, Tibor V
    et al.
    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
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Smoking status, snus use, and variation at the CHRNA5-CHRNA3-CHRNB4 locus in relation to obesity: the GLACIER study2013Ingår i: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 178, nr 1, s. 31-37Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A genetic variant within the CHRNA5-CHRNA3-CHRNB4 region (rs1051730), previously associated with smoking quantity, was recently shown to interact with smoking on obesity predisposition. We attempted to replicate this finding in the Gene-Lifestyle Interactions and Complex Traits Involved in Elevated Disease Risk (GLACIER) Study, a prospective cohort study of adults from northern Sweden (n = 16,426). We also investigated whether a similar interaction is apparent between rs1051730 and snus, a type of moist oral tobacco, to determine whether this interaction is driven by factors that cigarettes and snus have in common, such as nicotine. Main effects of smoking, snus, and the rs1051730 variant and pairwise interaction terms (smoking x rs1051730 and snus x rs1051730) were tested in relation to body mass index (BMI; calculated as weight (kg)/height (m)(2)) through the use of multivariate linear models adjusted for age and sex. Smoking status and BMI were inversely related (beta = -0.46 kg/m(2), standard error (SE) = 0.08; P < 0.0001). Snus use and BMI were positively related (beta = 0.35 kg/m(2), SE = 0.12; P = 0.003). The rs1051730 variant was not significantly associated with smoking status or snus use (P > 0.05); the T allele was associated with lower BMI in the overall cohort (beta = -0.10 kg/m(2), SE = 0.05; P = 0.03) and with smoking quantity in those in whom this was measured (n = 5,304) (beta = 0.08, SE = 0.01; P < 0.0001). Neither smoking status (P-interaction = 0.29) nor snus use (P-interaction = 0.89) modified the association between the rs1051730 variant and BMI.

  • 222. Varga, Tibor V.
    et al.
    Kurbasic, Azra
    Aine, Mattias
    Eriksson, Pontus
    Ali, Ashfaq
    Hindy, George
    Gustafsson, Stefan
    Luan, Jian'an
    Shungin, Dmitry
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi. Lund Univ, Skane Univ Hosp, Malmo, Sweden.
    Chen, Yan
    Schulz, Christina-Alexandra
    Nilsson, Peter M.
    Hallmans, Goran
    Barroso, Ines
    Deloukas, Panos
    Langenberg, Claudia
    Scott, Robert A.
    Wareham, Nicholas J.
    Lind, Lars
    Ingelsson, Erik
    Melander, Olle
    Orho-Melander, Marju
    Renström, Frida
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Lund Univ, Skane Univ Hosp, Malmo, Sweden.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Lund Univ, Skane Univ Hosp, Malmo, Sweden ; Harvard, Boston, MA USA.
    Novel genetic loci associated with long-term deterioration in blood lipid concentrations and coronary artery disease in European adults2017Ingår i: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 46, nr 4, s. 1211-1222Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Cross-sectional genome-wide association studies have identified hundreds of loci associated with blood lipids and related cardiovascular traits, but few genetic association studies have focused on long-term changes in blood lipids. Methods: Participants from the GLACIER Study (N-max = 3492) were genotyped with the MetaboChip array, from which 29 387 SNPs (single nucleotide polymorphisms;replication, fine-mapping regions and wildcard SNPs for lipid traits) were extracted for association tests with 10-year change in total cholesterol (Delta TC) and triglycerides (Delta TG). Four additional prospective cohort studies (MDC, PIVUS, ULSAM, MRC Ely; N-max = 8263 participants) were used for replication. We conducted an in silico look-up for association with coronary artery disease (CAD) in the Coronary ARtery DIsease Genome-wide Replication and Meta-analysis (CARDIoGRAMplusC4D) Consortium (N similar to 190 000) and functional annotation for the top ranking variants. Results: In total, 956 variants were associated (P < 0.01) with either Delta TC or Delta TG in GLACIER. In GLACIER, chr19:50121999 at APOE was associated with Delta TG and multiple SNPs in the APOA1/A4/C3/A5 region at genome-wide significance (P < 5 x 10(-8)), whereas variants in four loci, DOCK7, BRE, SYNE1 and KCNIP1, reached study-wide significance (P < 1.7 x 10(-6)). The rs7412 variant at APOE was associated with DTC in GLACIER (P < 1.7 x 10(-6)). In pooled analyses of all cohorts, 139 SNPs at six and five loci were associated with Delta TC and for Delta TG, respectively (P < 10(-3)). Of these, a variant at CAPN3 (P = 1.2 x 10(-4)), multiple variants at HPR (P-min = 1.5 x 10(-6)) and a variant at SIX5 (P = 1.9 x 10(-4)) showed evidence for association with CAD. Conclusions: We identified seven novel genomic regions associated with long-term changes in blood lipids, of which three also raise CAD risk.

  • 223. Varga, Tibor V.
    et al.
    Sonestedt, Emily
    Shungin, Dmitry
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi. 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.
    Koivula, Robert W.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Andersson Escher, Stefan
    Barroso, Ines
    Nilsson, Peter
    Melander, Olle
    Orho-Melander, Marju
    Renström, Frida
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Skåne University Hospital Malmö, 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, Skåne University Hospital Malmö, Malmö, Sweden ; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA.
    Genetic determinants of long-term changes in blood lipid concentrations: 10-year follow-up of the GLACIER study2014Ingår i: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 10, nr 6, s. e1004388-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Recent genome-wide meta-analyses identified 157 loci associated with cross-sectional lipid traits. Here we tested whether these loci associate (singly and in trait-specific genetic risk scores [GRS]) with longitudinal changes in total cholesterol (TC) and triglyceride (TG) levels in a population-based prospective cohort from Northern Sweden (the GLACIER Study). We sought replication in a southern Swedish cohort (the MDC Study; N = 2,943). GLACIER Study participants (N = 6,064) were genotyped with the MetaboChip array. Up to 3,495 participants had 10-yr follow-up data available in the GLACIER Study. The TC- and TG-specific GRSs were strongly associated with change in lipid levels (beta = 0.02 mmol/l per effect allele per decade follow-up, P = 2.0x10(-11) for TC; beta = 0.02 mmol/l per effect allele per decade follow-up, P = 5.0x10(-5) for TG). In individual SNP analysis, one TC locus, apolipoprotein E (APOE) rs4420638 (beta = 0.12 mmol/l per effect allele per decade follow-up, P = 2.0x10(-5)), and two TG loci, tribbles pseudokinase 1 (TRIB1) rs2954029 (beta = 0.09 mmol/l per effect allele per decade follow-up, P = 5.1x10(-4)) and apolipoprotein A-I (APOA1) rs6589564 (beta = 0.31 mmol/l per effect allele per decade follow-up, P = 1.4x10(-8)), remained significantly associated with longitudinal changes for the respective traits after correction for multiple testing. An additional 12 loci were nominally associated with TC or TG changes. In replication analyses, the APOE rs4420638, TRIB1 rs2954029, and APOA1 rs6589564 associations were confirmed (P <= 0.001). In summary, trait-specific GRSs are robustly associated with 10-yr changes in lipid levels and three individual SNPs were strongly associated with 10-yr changes in lipid levels.

  • 224. Varga, Tibor V.
    et al.
    Winters, Alexandra H.
    Jablonski, Kathleen A.
    Horton, Edward S.
    Khare-Ranade, Prajakta
    Knowler, William C.
    Marcovina, Santica M.
    Renström, Frida
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden.
    Watson, Karol E.
    Goldberg, Ronald
    Florez, José C.
    Pollin, Toni I.
    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, Sweden; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.
    Comprehensive Analysis of Established Dyslipidemia-Associated Loci in the Diabetes Prevention Program2016Ingår i: Circulation: Cardiovascular Genetics, ISSN 1942-325X, E-ISSN 1942-3268, Vol. 9, nr 6, s. 495-503Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: We assessed whether 234 established dyslipidemia-associated loci modify the effects of metformin treatment and lifestyle intervention (versus placebo control) on lipid and lipid subfraction levels in the Diabetes Prevention Program randomized controlled trial. Methods and Results: We tested gene treatment interactions in relation to baseline-adjusted follow-up blood lipid concentrations (high-density lipoprotein [HDL] and low-density lipoprotein-cholesterol, total cholesterol, and triglycerides) and lipoprotein subfraction particle concentrations and size in 2993 participants with pre-diabetes. Of the previously reported single-nucleotide polymorphism associations, 32.5% replicated at P<0.05 with baseline lipid traits. Trait-specific genetic risk scores were robustly associated (3x10(-4)>P>1.1x10(-16)) with their respective baseline traits for all but 2 traits. Lifestyle modified the effect of the genetic risk score for large HDL particle numbers, such that each risk allele of the genetic risk scores was associated with lower concentrations of large HDL particles at follow-up in the lifestyle arm (beta=-0.11 mu mol/L per genetic risk scores risk allele; 95% confidence interval, -0.188 to -0.033; P=5x10(-3); P-interaction=1x10(-3) for lifestyle versus placebo), but not in the metformin or placebo arms (P>0.05). In the lifestyle arm, participants with high genetic risk had more favorable or similar trait levels at 1-year compared with participants at lower genetic risk at baseline for 17 of the 20 traits. Conclusions: Improvements in large HDL particle concentrations conferred by lifestyle may be diminished by genetic factors. Lifestyle intervention, however, was successful in offsetting unfavorable genetic loading for most lipid traits.

  • 225. Venti, Colleen A
    et al.
    Votruba, Susanne B
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Krakoff, Jonathan
    Salbe, Arline D
    Reproducibility of ad libitum energy intake with the use of a computerized vending machine system2010Ingår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 91, nr 2, s. 343-348Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Although ad libitum energy intake exceeded %WMEN, the within-person reliability of this intake across multiple visits was high, which makes this a reproducible method for the measurement of ad libitum intake in subjects who reside in a research unit. This trial was registered at clinicaltrials.gov as NCT00342732.

  • 226. Vimaleswaran, Karani S
    et al.
    Franks, Paul
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Brage, Soren
    Sardinha, Luis B
    Andersen, Lars B
    Wareham, Nicholas J
    Ekelund, Ulf
    Loos, Ruth J F
    Absence of association between the INSIG2 gene polymorphism (rs7566605) and obesity in the European Youth Heart Study (EYHS)2009Ingår i: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 17, nr 7, s. 1453-1457Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The first genome-wide association study for BMI identified a polymorphism, rs7566605, 10 kb upstream of the insulin-induced gene 2 (INSIG2) transcription start site, as the most significantly associated variant in children and adults. Subsequent studies, however, showed inconsistent association of this polymorphism with obesity traits. This polymorphism has been hypothesized to alter INSIG2 expression leading to inhibition of fatty acid and cholesterol synthesis. Hence, we investigated the association of the INSIG2 rs7566605 polymorphism with obesity- and lipid-related traits in Danish and Estonian children (930 boys and 1,073 girls) from the European Youth Heart Study (EYHS), a school-based, cross-sectional study of pre- and early pubertal children. The association between the polymorphism and obesity traits was tested using additive and recessive models adjusted for age, age-group, gender, maturity and country. Interactions were tested by including the interaction terms in the model. Despite having sufficient power (98%) to detect the previously reported effect size for association with BMI, we did not find significant effects of rs7566605 on BMI (additive, P = 0.68; recessive, P = 0.24). Accordingly, the polymorphism was not associated with overweight (P = 0.87) or obesity (P = 0.34). We also did not find association with waist circumference (WC), sum of four skinfolds, or with total cholesterol, triglycerides, low-density lipoprotein, or high-density lipoprotein. There were no gender-specific (P = 0.55), age-group-specific (P = 0.63) or country-specific (P = 0.56) effects. There was also no evidence of interaction between genotype and physical activity (P = 0.95). Despite an adequately powered study, our findings suggest that rs7566605 is not associated with obesity-related traits and lipids in the EYHS.Obesity (2009) doi:10.1038/oby.2008.650.

  • 227. Vimaleswaran, Karani S.
    et al.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Medical Research Council Epidemiology Unit, Institute of Metabolic Science, Cambridge, UK.
    Barroso, Inês
    Brage, Soren
    Ekelund, Ulf
    Wareham, Nicholas J.
    Loos, Ruth J. F.
    Habitual Energy Expenditure Modifies the Association Between NOS3 Gene Polymorphisms and Blood Pressure2008Ingår i: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 21, nr 3, s. 297-302Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The endothelial nitric-oxide synthase (NOS3) gene encodes the enzyme (eNOS) that synthesizes the molecule nitric oxide, which facilitates endothelium-dependent vasodilation in response to physical activity. Thus, energy expenditure may modify the association between the genetic variation at NOS3and blood pressure.

    Methods: To test this hypothesis, we genotyped 11 NOS3 polymorphisms, capturing all common variations, in 726 men and women from the Medical Research Council (MRC) Ely Study (age (mean ± s.d.): 55 ± 10 years, body mass index: 26.4 ± 4.1 kg/m2). Habitual/non-resting energy expenditure (NREE) was assessed via individually calibrated heart rate monitoring over 4 days.

    Results: The intronic variant, IVS25+15 [G→A], was significantly associated with blood pressure; GG homozygotes had significantly lower levels of diastolic blood pressure (DBP) (−2.8 mm Hg; P = 0.016) and systolic blood pressure (SBP) (−1.9 mm Hg; P = 0.018) than A-allele carriers. The interaction between NREE and IVS25+15 was also significant for both DBP (P = 0.006) and SBP (P = 0.026), in such a way that the effect of the GG-genotype on blood pressure was stronger in individuals with higher NREE (DBP: −4.9 mm Hg, P = 0.02. SBP: −3.8 mm Hg, P= 0.03 for the third tertile). Similar results were observed when the outcome was dichotomously defined as hypertension.

    Conclusions: In summary, the NOS3 IVS25+15 is directly associated with blood pressure and hypertension in white Europeans. However, the associations are most evident in the individuals with the highest NREE. These results need further replication and have to be ideally tested in a trial before being informative for targeted disease prevention. Eventually, the selection of individuals for lifestyle intervention programs could be guided by knowledge of genotype.

  • 228. Vimaleswaran, Karani S
    et al.
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Brage, Sören
    Gröntved, Anders
    Wareham, Nicholas J
    Ekelund, Ulf
    Loos, Ruth J F
    Lack of association between PCK1 polymorphisms and obesity, physical activity, and fitness in European Youth Heart Study (EYHS)2010Ingår i: Obesity (Silver Spring, Md.), ISSN 1930-7381, Vol. 18, nr 10, s. 1975-1980Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Phosphoenolpyruvate carboxykinase-1 (PCK1) is the rate-limiting enzyme in the hepatic gluconeogenic pathway. Studies have shown that overexpression of Pck1 in mice results in obesity-related traits and higher levels of physical activity (PA). Therefore, our aims were to investigate whether common genetic variation in the PCK1 gene influences obesity-related traits, PA, and fitness, and to examine whether PA and fitness attenuate the influence of the PCK1 polymorphisms on obesity in children. Analyses were undertaken on data from Danish and Estonian children (958 boys and 1,104 girls) from the European Youth Heart Study (EYHS), a school-based, cross-sectional study of children (mean ± s.d. age: 9.6 ± 0.4 years) and adolescents (15.5 ± 0.5 years). We genotyped eight polymorphisms that captured the common genetic variations in the PCK1 gene. The association between the PCK1 polymorphisms and BMI, waist circumference (WC), sum of four skinfolds, PA, and fitness was tested using an additive model adjusted for age, age-group, gender, maturity, and country. Interactions were tested by including interaction terms in the model. None of the polymorphisms were significantly associated with BMI, WC, sum of four skinfolds, PA, and fitness, and also with the risk of being overweight or obese (P > 0.05). The interactions between the polymorphisms and age-group, gender, PA, and fitness were not statistically significant. This is the first study to comprehensively examine the association of PCK1 polymorphisms with obesity, PA, and fitness. Despite strong evidence from animal studies, our study in the EYHS cohort failed to identify an association of PCK1 polymorphisms with obesity, PA, and fitness.

  • 229. Vimaleswaran, Karani Santhanakrishnan
    et al.
    Luan, Jian'an
    Andersen, Gitte
    Muller, Y Li
    Wheeler, Eleanor
    Brito, Ema C
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    O'Rahilly, Stephen
    Pedersen, Oluf
    Baier, Leslie J
    Knowler, William C
    Barroso, Inês
    Wareham, Nicholas J
    Loos, Ruth J F
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Medical Research Council, Epidemiology Unit, Institute of Metabolic Science, Cambridge, United Kingdom.
    The Gly482Ser genotype at the PPARGC1A gene and elevated blood pressure: a meta-analysis involving 13,949 individuals2008Ingår i: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 105, nr 4, s. 1352-1358Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The protein encoded by the PPARGC1A gene is expressed at high levels in metabolically active tissues and is involved in the control of oxidative stress via reactive oxygen species detoxification. Several recent reports suggest that the PPARGC1A Gly482Ser (rs8192678) missense polymorphism may relate inversely with blood pressure. We used conventional meta-analysis methods to assess the association between Gly482Ser and systolic (SBP) or diastolic blood pressures (DBP) or hypertension in 13,949 individuals from 17 studies, of which 6,042 were previously unpublished observations. The studies comprised cohorts of white European, Asian, and American Indian adults, and adolescents from South America. Stratified analyses were conducted to control for population stratification. Pooled genotype frequencies were 0.47 (Gly482Gly), 0.42 (Gly482Ser), and 0.11 (Ser482Ser). We found no evidence of association between Gly482Ser and SBP [Gly482Gly: mean = 131.0 mmHg, 95% confidence interval (CI) = 130.5-131.5 mmHg; Gly482Ser mean = 133.1 mmHg, 95% CI = 132.6-133.6 mmHg; Ser482Ser: mean = 133.5 mmHg, 95% CI = 132.5-134.5 mmHg; P = 0.409] or DBP (Gly482Gly: mean = 80.3 mmHg, 95% CI = 80.0-80.6 mmHg; Gly482Ser mean = 81.5 mmHg, 95% CI = 81.2-81.8 mmHg; Ser482Ser: mean = 82.1 mmHg, 95% CI = 81.5-82.7 mmHg; P = 0.651). Contrary to previous reports, we did not observe significant effect modification by sex (SBP, P = 0.966; DBP, P = 0.715). We were also unable to confirm the previously reported association between the Ser482 allele and hypertension [odds ratio: 0.97, 95% CI = 0.87-1.08, P = 0.585]. These results were materially unchanged when analyses were focused on whites only. However, statistical evidence of gene-age interaction was apparent for DBP [Gly482Gly: 73.5 (72.8, 74.2), Gly482Ser: 77.0 (76.2, 77.8), Ser482Ser: 79.1 (77.4, 80.9), P = 4.20 x 10(-12)] and SBP [Gly482Gly: 121.4 (120.4, 122.5), Gly482Ser: 125.9 (124.6, 127.1), Ser482Ser: 129.2 (126.5, 131.9), P = 7.20 x 10(-12)] in individuals <50 yr (n = 2,511); these genetic effects were absent in those older than 50 yr (n = 5,088) (SBP, P = 0.41; DBP, P = 0.51). Our findings suggest that the PPARGC1A Ser482 allele may be associated with higher blood pressure, but this is only apparent in younger adults.

  • 230. Wessel, Jennifer
    et al.
    Chu, Audrey Y.
    Willems, Sara M.
    Wang, Shuai
    Yaghootkar, Hanieh
    Brody, Jennifer A.
    Dauriz, Marco
    Hivert, Marie-France
    Raghavan, Sridharan
    Lipovich, Leonard
    Hidalgo, Bertha
    Fox, Keolu
    Huffman, Jennifer E.
    An, Ping
    Lu, Yingchang
    Rasmussen-Torvik, Laura J.
    Grarup, Niels
    Ehm, Margaret G.
    Li, Li
    Baldridge, Abigail S.
    Stancakova, Alena
    Abrol, Ravinder
    Besse, Celine
    Boland, Anne
    Bork-Jensen, Jette
    Fornage, Myriam
    Freitag, Daniel F.
    Garcia, Melissa E.
    Guo, Xiuqing
    Hara, Kazuo
    Isaacs, Aaron
    Jakobsdottir, Johanna
    Lange, Leslie A.
    Layton, Jill C.
    Li, Man
    Zhao, Jing Hua
    Meidtner, Karina
    Morrison, Alanna C.
    Nalls, Mike A.
    Peters, Marjolein J.
    Sabater-Lleal, Maria
    Schurmann, Claudia
    Silveira, Angela
    Smith, Albert V.
    Southam, Lorraine
    Stoiber, Marcus H.
    Strawbridge, Rona J.
    Taylor, Kent D.
    Varga, Tibor V.
    Allin, Kristine H.
    Amin, Najaf
    Aponte, Jennifer L.
    Aung, Tin
    Barbieri, Caterina
    Bihlmeyer, Nathan A.
    Boehnke, Michael
    Bombieri, Cristina
    Bowden, Donald W.
    Burns, Sean M.
    Chen, Yuning
    Chen, Yii-Deri
    Cheng, Ching-Yu
    Correa, Adolfo
    Czajkowski, Jacek
    Dehghan, Abbas
    Ehret, Georg B.
    Eiriksdottir, Gudny
    Andersson Escher, Stefan
    Farmaki, Aliki-Eleni
    Franberg, Mattias
    Gambaro, Giovanni
    Giulianini, Franco
    Goddard, William A., III
    Goel, Anuj
    Gottesman, Omri
    Grove, Megan L.
    Gustafsson, Stefan
    Hai, Yang
    Hallmans, Goeran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Heo, Jiyoung
    Hoffmann, Per
    Ikram, Mohammad K.
    Jensen, Richard A.
    Jorgensen, Marit E.
    Jorgensen, Torben
    Karaleftheri, Maria
    Khor, Chiea C.
    Kirkpatrick, Andrea
    Kraja, Aldi T.
    Kuusisto, Johanna
    Lange, Ethan M.
    Lee, I. T.
    Lee, Wen-Jane
    Leong, Aaron
    Liao, Jiemin
    Liu, Chunyu
    Liu, Yongmei
    Lindgren, Cecilia M.
    Linneberg, Allan
    Malerba, Giovanni
    Mamakou, Vasiliki
    Marouli, Eirini
    Maruthur, Nisa M.
    Matchan, Angela
    McKean-Cowdin, Roberta
    McLeod, Olga
    Metcalf, Ginger A.
    Mohlke, Karen L.
    Muzny, Donna M.
    Ntalla, Ioanna
    Palmer, Nicholette D.
    Pasko, Dorota
    Peter, Andreas
    Rayner, Nigel W.
    Renstroem, Frida
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Rice, Ken
    Sala, Cinzia F.
    Sennblad, Bengt
    Serafetinidis, Ioannis
    Smith, Jennifer A.
    Soranzo, Nicole
    Speliotes, Elizabeth K.
    Stahl, Eli A.
    Stirrups, Kathleen
    Tentolouris, Nikos
    Thanopoulou, Anastasia
    Torres, Mina
    Traglia, Michela
    Tsafantakis, Emmanouil
    Javad, Sundas
    Yanek, Lisa R.
    Zengini, Eleni
    Becker, Diane M.
    Bis, Joshua C.
    Brown, James B.
    Cupples, L. Adrienne
    Hansen, Torben
    Ingelsson, Erik
    Karter, Andrew J.
    Lorenzo, Carlos
    Mathias, Rasika A.
    Norris, Jill M.
    Peloso, Gina M.
    Sheu, Wayne H. -H.
    Toniolo, Daniela
    Vaidya, Dhananjay
    Varma, Rohit
    Wagenknecht, Lynne E.
    Boeing, Heiner
    Bottinger, Erwin P.
    Dedoussis, George
    Deloukas, Panos
    Ferrannini, Ele
    Franco, Oscar H.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Gibbs, Richard A.
    Gudnason, Vilmundur
    Hamsten, Anders
    Harris, Tamara B.
    Hattersley, Andrew T.
    Hayward, Caroline
    Hofman, Albert
    Jansson, Jan-Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Langenberg, Claudia
    Launer, Lenore J.
    Levy, Daniel
    Oostra, Ben A.
    O'Donnell, Christopher J.
    O'Rahilly, Stephen
    Padmanabhan, Sandosh
    Pankow, James S.
    Polasek, Ozren
    Province, Michael A.
    Rich, Stephen S.
    Ridker, Paul M.
    Rudan, Igor
    Schulze, Matthias B.
    Smith, Blair H.
    Uitterlinden, Andre G.
    Walker, Mark
    Watkins, Hugh
    Wong, Tien Y.
    Zeggini, Eleftheria
    Laakso, Markku
    Borecki, Ingrid B.
    Chasman, Daniel I.
    Pedersen, Oluf
    Psaty, Bruce M.
    Tai, E. Shyong
    van Duijn, Cornelia M.
    Wareham, Nicholas J.
    Waterworth, Dawn M.
    Boerwinkle, Eric
    Kao, W. H. Linda
    Florez, Jose C.
    Loos, Ruth J. F.
    Wilson, James G.
    Frayling, Timothy M.
    Siscovick, David S.
    Dupuis, Josee
    Rotter, Jerome I.
    Meigs, James B.
    Scott, Robert A.
    Goodarzi, Mark O.
    Sharp, Stephen J.
    Forouhi, Nita G.
    Kerrison, Nicola D.
    Lucarelli, Debora M. E.
    Sims, Matt
    Barroso, Ines
    McCarthy, Mark I.
    Arriola, Larraitz
    Balkau, Beverley
    Barricarte, Aurelio
    Gonzalez, Carlos
    Grioni, Sara
    Kaaks, Rudolf
    Key, Timothy J.
    Navarro, Carmen
    Nilsson, Peter M.
    Overvad, Kim
    Palli, Domenico
    Panico, Salvatore
    Quiros, J. Ramon
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Sacerdote, Carlotta
    Sanchez, Maria-Jose
    Slimani, Nadia
    Tjonneland, Anne
    Tumino, Rosario
    van der A, Daphne L.
    van der Schouw, Yvonne T.
    Riboli, Elio
    Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility2015Ingår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 6, artikel-id 5897Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF = 1.4%) with lower FG (beta = -0.09 +/- 0.01 mmol l(-1), P = 3.4 x 10(-12)), T2D risk (OR[95% CI] = 0.86[0.76-0.96], P = 0.010), early insulin secretion (beta = -0.07 +/- 0.035 pmol(insulin) mmol(glucose)(-1), P = 0.048), but higher 2-h glucose (beta = 0.16 +/- 0.05 mmol l(-1), P = 4.3 x 10(-4)). We identify a gene-based association with FG at G6PC2 (p(SKAT) = 6.8 x 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF = 20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (beta = 0.02 +/- 0.004 mmol l(-1), P = 1.3 x 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.

  • 231. Wientzek, Angelika
    et al.
    Tormo Diaz, Maria-Jose
    Huerta Castano, Jose Maria
    Amiano, Pilar
    Arriola, Larraitz
    Overvad, Kim
    Ostergaard, Jane Nautrup
    Charles, Marie-Aline
    Fagherazzi, Guy
    Palli, Domenico
    Bendinelli, Benedetta
    Skeie, Guri
    Borch, Kristin Benjaminsen
    Wendel-Vos, Wanda
    de Hollander, Ellen
    May, Anne M.
    den Ouden, Marjolein E. M.
    Trichopoulou, Antonia
    Valanou, Elissavet
    Söderberg, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Brage, Soren
    Vigl, Matthaus
    Boeing, Heiner
    Ekelund, Ulf
    Cross-Sectional Associations of Objectively Measured Physical Activity, Cardiorespiratory Fitness and Anthropometry in European Adults2014Ingår i: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 22, nr 5, s. E127-E134Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To quantify the independent associations between objectively measured physical activity (PA), cardiorespiratory fitness (CRF), and anthropometry in European men and women. Methods: 2,056 volunteers from 12 centers across Europe were fitted with a heart rate and movement sensor at 2 visits 4 months apart for a total of 8 days. CRF (ml/kg/min) was estimated from an 8 minute ramped step test. A cross-sectional analysis of the independent associations between objectively measured PA (m/s(2)/d), moderate and vigorous physical activity (MVPA) (% time/d), sedentary time (% time/d), CRF, and anthropometry using sex stratified multiple linear regression was performed. Results: In mutually adjusted models, CRF, PA, and MVPA were inversely associated with all anthropometric markers in women. In men, CRF, PA, and MVPA were inversely associated with BMI, whereas only CRF was significantly associated with the other anthropometric markers. Sedentary time was positively associated with all anthropometric markers, however, after adjustment for CRF significant in women only. Conclusion: CRF, PA, MVPA, and sedentary time are differently associated with anthropometric markers in men and women. CRF appears to attenuate associations between PA, MVPA, and sedentary time. These observations may have implications for prevention of obesity.

  • 232.
    Wiklund, Peder
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin.
    Nordström, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    Högström, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    Alfredson, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    Engström, Patrik
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Gustafsson, Thomas
    Karolinska universitetslaboratoriet, Klinisk kemi.
    Franks, Paul
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Nordström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    High impact loading on the skeleton is associated with a decrease in glucose levels in young men2012Ingår i: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 77, nr 6, s. 823-827Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective The skeleton has been suggested to be involved in energy metabolism through osteocalcin (OC), an osteoblast-specific molecule. The objective of this study was to investigate whether high impact exercise stimulating bone formation would lead to changes in glucose and lipid metabolism independent of cardiorespiratory effects, and if OC mediates this association.

    Design Prospective intervention study.

    Methods Fifty men aged 20-32 years were allocated to an intervention group or a control group. The intervention group completed six different types of jumps in sets of five, with the frequency of these exercises gradually increasing over 8 weeks. At baseline and after 8 weeks, glycerol concentrations were measured in fat tissue as a marker of lipolysis by using microdialysis. Blood samples were assayed for OC and markers of glucose and lipid metabolism. Physical activity was measured using an accelerometer.

    Results After adjustment for confounders at baseline and changes in physical activity during the intervention period, the intervention was associated with a decrease in levels of glucose (p = 0.04), adrenalin (p = 0.03) and OC (p=0.04) after adjusting for baseline levels and changes in physical activity. No other differences between the groups were significant, although the trends of the metabolic variables favored the intervention group.

    Conclusions The results of this study suggest that high impact loading on the skeleton may affect glucose metabolism independent of the level of aerobic exercise.

  • 233.
    Wiklund, Peder
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Toss, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin.
    Jansson, Jan-Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Eliasson, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Nordström, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Nordström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin.
    Abdominal and gynoid adipose distribution and incident myocardial infarction in women and men2010Ingår i: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 34, nr 12, s. 1752-1758Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In summary, fat distribution was a strong predictor of the risk of MI in women, but not in men. These different results may be explained by the associations found between fat distribution and hypertension, impaired glucose tolerance and hypertriglyceridemia.

  • 234.
    Wiklund, Peder
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin.
    Toss, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Weinehall, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och folkhälsovetenskap.
    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, Medicin.
    Nordström, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin.
    Nordström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Abdominal and gynoid fat mass are associated with cardiovascular risk factors in men and women2008Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 93, nr 11, s. 4360-4366Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    CONTEXT: Abdominal obesity is an established risk factor for cardiovascular disease (CVD). However, the correlation of dual-energy x-ray absorptiometry (DEXA) measurements of regional fat mass with CVD risk factors has not been completely investigated.

    OBJECTIVE: The aim of this study was to investigate the association of estimated regional fat mass, measured with DEXA and CVD risk factors.

    DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional study of 175 men and 417 women. DEXA measurements of regional fat mass were performed on all subjects, who subsequently participated in a community intervention program.

    MAIN OUTCOME MEASURES: Outcome measures included impaired glucose tolerance, hypercholesterolemia, hypertriglyceridemia, and hypertension. RESULTS: We began by assessing the associations of the adipose measures with the cardiovascular outcomes. After adjustment for confounders, a sd unit increase in abdominal fat mass was the strongest predictor of most cardiovascular variables in men [odds ratio (OR)=2.63-3.37; P<0.05], whereas the ratio of abdominal to gynoid fat mass was the strongest predictor in women (OR=1.48-2.19; P<0.05). Gynoid fat mass was positively associated with impaired glucose tolerance, hypertriglyceridemia, and hypertension in men (OR=2.07-2.15; P<0.05), whereas the ratio of gynoid to total fat mass showed a negative association with hypertriglyceridemia and hypertension (OR=0.42-0.62; P<0.005).

    CONCLUSIONS: Abdominal fat mass is strongly independently associated with CVD risk factors in the present study. In contrast, gynoid fat mass was positively associated, whereas the ratio of gynoid to total fat mass was negatively associated with risk factors for CVD.

  • 235. Willems, Sara M.
    et al.
    Wright, Daniel J.
    Day, Felix R.
    Trajanoska, Katerina
    Joshi, Peter K.
    Morris, John A.
    Matteini, Amy M.
    Garton, Fleur C.
    Grarup, Niels
    Oskolkov, Nikolay
    Thalamuthu, Anbupalam
    Mangino, Massimo
    Liu, Jun
    Demirkan, Ayse
    Lek, Monkol
    Xu, Liwen
    Wang, Guan
    Oldmeadow, Christopher
    Gaulton, Kyle J.
    Lotta, Luca A.
    Miyamoto-Mikami, Eri
    Rivas, Manuel A.
    White, Tom
    Loh, Po-Ru
    Aadahl, Mette
    Amin, Najaf
    Attia, John R.
    Austin, Krista
    Benyamin, Beben
    Brage, Soren
    Cheng, Yu-Ching
    Cieszczyk, Pawel
    Derave, Wim
    Eriksson, Karl-Fredrik
    Eynon, Nir
    Linneberg, Allan
    Lucia, Alejandro
    Massidda, Myosotis
    Mitchell, Braxton D.
    Miyachi, Motohiko
    Murakami, Haruka
    Padmanabhan, Sandosh
    Pandey, Ashutosh
    Papadimitriou, Loannis
    Rajpal, Deepak K.
    Sale, Craig
    Schnurr, Theresia M.
    Sessa, Francesco
    Shrine, Nick
    Tobin, Martin D.
    Varley, Ian
    Wain, Louise V.
    Wray, Naomi R.
    Lindgren, Cecilia M.
    MacArthur, Daniel G.
    Waterworth, Dawn M.
    McCarthy, Mark I.
    Pedersen, Oluf
    Khaw, Kay-Tee
    Kie, Douglas P.
    Pitsiladis, Yannis
    Fuku, Noriyuki
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Lund University, Skånes University Hospital, 222 41 Lund, Sweden.
    North, Kathryn N.
    van Duijn, Cornelia M.
    Mather, Karen A.
    Hansen, Torben
    Hansson, Ola
    Spector, Tim
    Murabito, Joanne M.
    Richards, J. Brent
    Rivadeneira, Fernando
    Langenberg, Claudia
    Perry, John R. B.
    Wareham, Nick J.
    Scott, Robert A.
    Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness2017Ingår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 8, artikel-id 16015Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Hand grip strength is a widely used proxy of muscular fitness, a marker of frailty, and predictor of a range of morbidities and all-cause mortality. To investigate the genetic determinants of variation in grip strength, we perform a large-scale genetic discovery analysis in a combined sample of 195,180 individuals and identify 16 loci associated with grip strength (P<5 x 10(-8)) in combined analyses. A number of these loci contain genes implicated in structure and function of skeletal muscle fibres (ACTG1), neuronal maintenance and signal transduction (PEX14, TGFA, SYT1), or monogenic syndromes with involvement of psychomotor impairment (PEX14, LRPPRC and KANSL1). Mendelian randomization analyses are consistent with a causal effect of higher genetically predicted grip strength on lower fracture risk. In conclusion, our findings provide new biological insight into the mechanistic underpinnings of grip strength and the causal role of muscular strength in age-related morbidities and mortality.

  • 236. Willer, Cristen J.
    et al.
    Schmidt, Ellen M.
    Sengupta, Sebanti
    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.
    Do, Ron
    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.
    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
    Kathiresan, Sekar
    Mohlke, Karen L.
    Ingelsson, Erik
    Abecasis, Goncalo R.
    Discovery and refinement of loci associated with lipid levels2013Ingår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 45, nr 11, s. 1274-+Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 x 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.

  • 237. Winkler, Thomas W
    et al.
    Justice, Anne E
    Graff, Mariaelisa
    Barata, Llilda
    Feitosa, Mary F
    Chu, Su
    Czajkowski, Jacek
    Esko, Tõnu
    Fall, Tove
    Kilpeläinen, Tuomas O
    Lu, Yingchang
    Mägi, Reedik
    Mihailov, Evelin
    Pers, Tune H
    Rüeger, Sina
    Teumer, Alexander
    Ehret, Georg B
    Ferreira, Teresa
    Heard-Costa, Nancy L
    Karjalainen, Juha
    Lagou, Vasiliki
    Mahajan, Anubha
    Neinast, Michael D
    Prokopenko, Inga
    Simino, Jeannette
    Teslovich, Tanya M
    Jansen, Rick
    Westra, Harm-Jan
    White, Charles C
    Absher, Devin
    Ahluwalia, Tarunveer S
    Ahmad, Shafqat
    Albrecht, Eva
    Alves, Alexessander Couto
    Bragg-Gresham, Jennifer L
    de Craen, Anton J M
    Bis, Joshua C
    Bonnefond, Amélie
    Boucher, Gabrielle
    Cadby, Gemma
    Cheng, Yu-Ching
    Chiang, Charleston W K
    Delgado, Graciela
    Demirkan, Ayse
    Dueker, Nicole
    Eklund, Niina
    Eiriksdottir, Gudny
    Eriksson, Joel
    Feenstra, Bjarke
    Fischer, Krista
    Frau, Francesca
    Galesloot, Tessel E
    Geller, Frank
    Goel, Anuj
    Gorski, Mathias
    Grammer, Tanja B
    Gustafsson, Stefan
    Haitjema, Saskia
    Hottenga, Jouke-Jan
    Huffman, Jennifer E
    Jackson, Anne U
    Jacobs, Kevin B
    Johansson, Åsa
    Kaakinen, Marika
    Kleber, Marcus E
    Lahti, Jari
    Mateo Leach, Irene
    Lehne, Benjamin
    Liu, Youfang
    Lo, Ken Sin
    Lorentzon, Mattias
    Luan, Jian'an
    Madden, Pamela A F
    Mangino, Massimo
    McKnight, Barbara
    Medina-Gomez, Carolina
    Monda, Keri L
    Montasser, May E
    Müller, Gabriele
    Müller-Nurasyid, Martina
    Nolte, Ilja M
    Panoutsopoulou, Kalliope
    Pascoe, Laura
    Paternoster, Lavinia
    Rayner, Nigel W
    Renström, Frida
    Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Skåne University Hospital Malmö, Malmö, Sweden.
    Rizzi, Federica
    Rose, Lynda M
    Ryan, Kathy A
    Salo, Perttu
    Sanna, Serena
    Scharnagl, Hubert
    Shi, Jianxin
    Smith, Albert Vernon
    Southam, Lorraine
    Stančáková, Alena
    Steinthorsdottir, Valgerdur
    Strawbridge, Rona J
    Sung, Yun Ju
    Tachmazidou, Ioanna
    Tanaka, Toshiko
    Thorleifsson, Gudmar
    Trompet, Stella
    Pervjakova, Natalia
    Tyrer, Jonathan P
    Vandenput, Liesbeth
    van der Laan, Sander W
    van der Velde, Nathalie
    van Setten, Jessica
    van Vliet-Ostaptchouk, Jana V
    Verweij, Niek
    Vlachopoulou, Efthymia
    Waite, Lindsay L
    Wang, Sophie R
    Wang, Zhaoming
    Wild, Sarah H
    Willenborg, Christina
    Wilson, James F
    Wong, Andrew
    Yang, Jian
    Yengo, Loïc
    Yerges-Armstrong, Laura M
    Yu, Lei
    Zhang, Weihua
    Zhao, Jing Hua
    Andersson, Ehm A
    Bakker, Stephan J L
    Baldassarre, Damiano
    Banasik, Karina
    Barcella, Matteo
    Barlassina, Cristina
    Bellis, Claire
    Benaglio, Paola
    Blangero, John
    Blüher, Matthias
    Bonnet, Fabrice
    Bonnycastle, Lori L
    Boyd, Heather A
    Bruinenberg, Marcel
    Buchman, Aron S
    Campbell, Harry
    Chen, Yii-Der Ida
    Chines, Peter S
    Claudi-Boehm, Simone
    Cole, John
    Collins, Francis S
    de Geus, Eco J C
    de Groot, Lisette C P G M
    Dimitriou, Maria
    Duan, Jubao
    Enroth, Stefan
    Eury, Elodie
    Farmaki, Aliki-Eleni
    Forouhi, Nita G
    Friedrich, Nele
    Gejman, Pablo V
    Gigante, Bruna
    Glorioso, Nicola
    Go, Alan S
    Gottesman, Omri
    Gräßler, Jürgen
    Grallert, Harald
    Grarup, Niels
    Gu, Yu-Mei
    Broer, Linda
    Ham, Annelies C
    Hansen, Torben
    Harris, Tamara B
    Hartman, Catharina A
    Hassinen, Maija
    Hastie, Nicholas
    Hattersley, Andrew T
    Heath, Andrew C
    Henders, Anjali K
    Hernandez, Dena
    Hillege, Hans
    Holmen, Oddgeir
    Hovingh, Kees G
    Hui, Jennie
    Husemoen, Lise L
    Hutri-Kähönen, Nina
    Hysi, Pirro G
    Illig, Thomas
    De Jager, Philip L
    Jalilzadeh, Shapour
    Jørgensen, Torben
    Jukema, J Wouter
    Juonala, Markus
    Kanoni, Stavroula
    Karaleftheri, Maria
    Khaw, Kay Tee
    Kinnunen, Leena
    Kittner, Steven J
    Koenig, Wolfgang
    Kolcic, Ivana
    Kovacs, Peter
    Krarup, Nikolaj T
    Kratzer, Wolfgang
    Krüger, Janine
    Kuh, Diana
    Kumari, Meena
    Kyriakou, Theodosios
    Langenberg, Claudia
    Lannfelt, Lars
    Lanzani, Chiara
    Lotay, Vaneet
    Launer, Lenore J
    Leander, Karin
    Lindström, Jaana
    Linneberg, Allan
    Liu, Yan-Ping
    Lobbens, Stéphane
    Luben, Robert
    Lyssenko, Valeriya
    Männistö, Satu
    Magnusson, Patrik K
    McArdle, Wendy L
    Menni, Cristina
    Merger, Sigrun
    Milani, Lili
    Montgomery, Grant W
    Morris, Andrew P
    Narisu, Narisu
    Nelis, Mari
    Ong, Ken K
    Palotie, Aarno
    Pérusse, Louis
    Pichler, Irene
    Pilia, Maria G
    Pouta, Anneli
    Rheinberger, Myriam
    Ribel-Madsen, Rasmus
    Richards, Marcus
    Rice, Kenneth M
    Rice, Treva K
    Rivolta, Carlo
    Salomaa, Veikko
    Sanders, Alan R
    Sarzynski, Mark A
    Scholtens, Salome
    Scott, Robert A
    Scott, William R
    Sebert, Sylvain
    Sengupta, Sebanti
    Sennblad, Bengt
    Seufferlein, Thomas
    Silveira, Angela
    Slagboom, P Eline
    Smit, Jan H
    Sparsø, Thomas H
    Stirrups, Kathleen
    Stolk, Ronald P
    Stringham, Heather M
    Swertz, Morris A
    Swift, Amy J
    Syvänen, Ann-Christine
    Tan, Sian-Tsung
    Thorand, Barbara
    Tönjes, Anke
    Tremblay, Angelo
    Tsafantakis, Emmanouil
    van der Most, Peter J
    Völker, Uwe
    Vohl, Marie-Claude
    Vonk, Judith M
    Waldenberger, Melanie
    Walker, Ryan W
    Wennauer, Roman
    Widén, Elisabeth
    Willemsen, Gonneke
    Wilsgaard, Tom
    Wright, Alan F
    Zillikens, M Carola
    van Dijk, Suzanne C
    van Schoor, Natasja M
    Asselbergs, Folkert W
    de Bakker, Paul I W
    Beckmann, Jacques S
    Beilby, John
    Bennett, David A
    Bergman, Richard N
    Bergmann, Sven
    Böger, Carsten A
    Boehm, Bernhard O
    Boerwinkle, Eric
    Boomsma, Dorret I
    Bornstein, Stefan R
    Bottinger, Erwin P
    Bouchard, Claude
    Chambers, John C
    Chanock, Stephen J
    Chasman, Daniel I
    Cucca, Francesco
    Cusi, Daniele
    Dedoussis, George
    Erdmann, Jeanette
    Eriksson, Johan G
    Evans, Denis A
    de Faire, Ulf
    Farrall, Martin
    Ferrucci, Luigi
    Ford, Ian
    Franke, Lude
    Franks, Paul W
    Umeå University Hospital; Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Skåne University Hospital Malmö, Malmö, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, United States of America .
    Froguel, Philippe
    Gansevoort, Ron T
    Gieger, Christian
    Grönberg, Henrik
    Gudnason, Vilmundur
    Gyllensten, Ulf
    Hall, Per
    Hamsten, Anders
    van der Harst, Pim
    Hayward, Caroline
    Heliövaara, Markku
    Hengstenberg, Christian
    Hicks, Andrew A
    Hingorani, Aroon
    Hofman, Albert
    Hu, Frank
    Huikuri, Heikki V
    Hveem, Kristian
    James, Alan L
    Jordan, Joanne M
    Jula, Antti
    Kähönen, Mika
    Kajantie, Eero
    Kathiresan, Sekar
    Kiemeney, Lambertus A L M
    Kivimaki, Mika
    Knekt, Paul B
    Koistinen, Heikki A
    Kooner, Jaspal S
    Koskinen, Seppo
    Kuusisto, Johanna
    Maerz, Winfried
    Martin, Nicholas G
    Laakso, Markku
    Lakka, Timo A
    Lehtimäki, Terho
    Lettre, Guillaume
    Levinson, Douglas F
    Lind, Lars
    Lokki, Marja-Liisa
    Mäntyselkä, Pekka
    Melbye, Mads
    Metspalu, Andres
    Mitchell, Braxton D
    Moll, Frans L
    Murray, Jeffrey C
    Musk, Arthur W
    Nieminen, Markku S
    Njølstad, Inger
    Ohlsson, Claes
    Oldehinkel, Albertine J
    Oostra, Ben A
    Palmer, Lyle J
    Pankow, James S
    Pasterkamp, Gerard
    Pedersen, Nancy L
    Pedersen, Oluf
    Penninx, Brenda W
    Perola, Markus
    Peters, Annette
    Polašek, Ozren
    Pramstaller, Peter P
    Psaty, Bruce M
    Qi, Lu
    Quertermous, Thomas
    Raitakari, Olli T
    Rankinen, Tuomo
    Rauramaa, Rainer
    Ridker, Paul M
    Rioux, John D
    Rivadeneira, Fernando
    Rotter, Jerome I
    Rudan, Igor
    den Ruijter, Hester M
    Saltevo, Juha
    Sattar, Naveed
    Schunkert, Heribert
    Schwarz, Peter E H
    Shuldiner, Alan R
    Sinisalo, Juha
    Snieder, Harold
    Sørensen, Thorkild I A
    Spector, Tim D
    Staessen, Jan A
    Stefania, Bandinelli
    Thorsteinsdottir, Unnur
    Stumvoll, Michael
    Tardif, Jean-Claude
    Tremoli, Elena
    Tuomilehto, Jaakko
    Uitterlinden, André G
    Uusitupa, Matti
    Verbeek, André L M
    Vermeulen, Sita H
    Viikari, Jorma S
    Vitart, Veronique
    Völzke, Henry
    Vollenweider, Peter
    Waeber, Gérard
    Walker, Mark
    Wallaschofski, Henri
    Wareham, Nicholas J
    Watkins, Hugh
    Zeggini, Eleftheria
    Chakravarti, Aravinda
    Clegg, Deborah J
    Cupples, L Adrienne
    Gordon-Larsen, Penny
    Jaquish, Cashell E
    Rao, D C
    Abecasis, Goncalo R
    Assimes, Themistocles L
    Barroso, Inês
    Berndt, Sonja I
    Boehnke, Michael
    Deloukas, Panos
    Fox, Caroline S
    Groop, Leif C
    Hunter, David J
    Ingelsson, Erik
    Kaplan, Robert C
    McCarthy, Mark I
    Mohlke, Karen L
    O'Connell, Jeffrey R
    Schlessinger, David
    Strachan, David P
    Stefansson, Kari
    van Duijn, Cornelia M
    Hirschhorn, Joel N
    Lindgren, Cecilia M
    Heid, Iris M
    North, Kari E
    Borecki, Ingrid B
    Kutalik, Zoltán
    Loos, Ruth J F
    The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study2015Ingår i: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 11, nr 10, artikel-id e1005378Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR<5%) age-specific effects, of which 11 had larger effects in younger (<50y) than in older adults (≥50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may provide further insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.

  • 238. Wood, Andrew R
    et al.
    Esko, Tonu
    Yang, Jian
    Vedantam, Sailaja
    Pers, Tune H
    Gustafsson, Stefan
    Chu, Audrey Y
    Estrada, Karol
    Luan, Jian'an
    Kutalik, Zoltán
    Amin, Najaf
    Buchkovich, Martin L
    Croteau-Chonka, Damien C
    Day, Felix R
    Duan, Yanan
    Fall, Tove
    Fehrmann, Rudolf
    Ferreira, Teresa
    Jackson, Anne U
    Karjalainen, Juha
    Lo, Ken Sin
    Locke, Adam E
    Mägi, Reedik
    Mihailov, Evelin
    Porcu, Eleonora
    Randall, Joshua C
    Scherag, André
    Vinkhuyzen, Anna A E
    Westra, Harm-Jan
    Winkler, Thomas W
    Workalemahu, Tsegaselassie
    Zhao, Jing Hua
    Absher, Devin
    Albrecht, Eva
    Anderson, Denise
    Baron, Jeffrey
    Beekman, Marian
    Demirkan, Ayse
    Ehret, Georg B
    Feenstra, Bjarke
    Feitosa, Mary F
    Fischer, Krista
    Fraser, Ross M
    Goel, Anuj
    Gong, Jian
    Justice, Anne E
    Kanoni, Stavroula
    Kleber, Marcus E
    Kristiansson, Kati
    Lim, Unhee
    Lotay, Vaneet
    Lui, Julian C
    Mangino, Massimo
    Mateo Leach, Irene
    Medina-Gomez, Carolina
    Nalls, Michael A
    Nyholt, Dale R
    Palmer, Cameron D
    Pasko, Dorota
    Pechlivanis, Sonali
    Prokopenko, Inga
    Ried, Janina S
    Ripke, Stephan
    Shungin, Dmitry
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Center, Skåne University Hospital, Malmö, Sweden.
    Stancáková, Alena
    Strawbridge, Rona J
    Sung, Yun Ju
    Tanaka, Toshiko
    Teumer, Alexander
    Trompet, Stella
    van der Laan, Sander W
    van Setten, Jessica
    Van Vliet-Ostaptchouk, Jana V
    Wang, Zhaoming
    Yengo, Loïc
    Zhang, Weihua
    Afzal, Uzma
    Arnlöv, Johan
    Arscott, Gillian M
    Bandinelli, Stefania
    Barrett, Amy
    Bellis, Claire
    Bennett, Amanda J
    Berne, Christian
    Blüher, Matthias
    Bolton, Jennifer L
    Böttcher, Yvonne
    Boyd, Heather A
    Bruinenberg, Marcel
    Buckley, Brendan M
    Buyske, Steven
    Caspersen, Ida H
    Chines, Peter S
    Clarke, Robert
    Claudi-Boehm, Simone
    Cooper, Matthew
    Daw, E Warwick
    De Jong, Pim A
    Deelen, Joris
    Delgado, Graciela
    Denny, Josh C
    Dhonukshe-Rutten, Rosalie
    Dimitriou, Maria
    Doney, Alex S F
    Dörr, Marcus
    Eklund, Niina
    Eury, Elodie
    Folkersen, Lasse
    Garcia, Melissa E
    Geller, Frank
    Giedraitis, Vilmantas
    Go, Alan S
    Grallert, Harald
    Grammer, Tanja B
    Gräßler, Jürgen
    Grönberg, Henrik
    de Groot, Lisette C P G M
    Groves, Christopher J
    Haessler, Jeffrey
    Hall, Per
    Haller, Toomas
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Hannemann, Anke
    Hartman, Catharina A
    Hassinen, Maija
    Hayward, Caroline
    Heard-Costa, Nancy L
    Helmer, Quinta
    Hemani, Gibran
    Henders, Anjali K
    Hillege, Hans L
    Hlatky, Mark A
    Hoffmann, Wolfgang
    Hoffmann, Per
    Holmen, Oddgeir
    Houwing-Duistermaat, Jeanine J
    Illig, Thomas
    Isaacs, Aaron
    James, Alan L
    Jeff, Janina
    Johansen, Berit
    Johansson, Asa
    Jolley, Jennifer
    Juliusdottir, Thorhildur
    Junttila, Juhani
    Kho, Abel N
    Kinnunen, Leena
    Klopp, Norman
    Kocher, Thomas
    Kratzer, Wolfgang
    Lichtner, Peter
    Lind, Lars
    Lindström, Jaana
    Lobbens, Stéphane
    Lorentzon, Mattias
    Lu, Yingchang
    Lyssenko, Valeriya
    Magnusson, Patrik K E
    Mahajan, Anubha
    Maillard, Marc
    McArdle, Wendy L
    McKenzie, Colin A
    McLachlan, Stela
    McLaren, Paul J
    Menni, Cristina
    Merger, Sigrun
    Milani, Lili
    Moayyeri, Alireza
    Monda, Keri L
    Morken, Mario A
    Müller, Gabriele
    Müller-Nurasyid, Martina
    Musk, Arthur W
    Narisu, Narisu
    Nauck, Matthias
    Nolte, Ilja M
    Nöthen, Markus M
    Oozageer, Laticia
    Pilz, Stefan
    Rayner, Nigel W
    Renström, Frida
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Center, Skåne University Hospital, Malmö, Sweden.
    Robertson, Neil R
    Rose, Lynda M
    Roussel, Ronan
    Sanna, Serena
    Scharnagl, Hubert
    Scholtens, Salome
    Schumacher, Fredrick R
    Schunkert, Heribert
    Scott, Robert A
    Sehmi, Joban
    Seufferlein, Thomas
    Shi, Jianxin
    Silventoinen, Karri
    Smit, Johannes H
    Smith, Albert Vernon
    Smolonska, Joanna
    Stanton, Alice V
    Stirrups, Kathleen
    Stott, David J
    Stringham, Heather M
    Sundström, Johan
    Swertz, Morris A
    Syvänen, Ann-Christine
    Tayo, Bamidele O
    Thorleifsson, Gudmar
    Tyrer, Jonathan P
    van Dijk, Suzanne
    van Schoor, Natasja M
    van der Velde, Nathalie
    van Heemst, Diana
    van Oort, Floor V A
    Vermeulen, Sita H
    Verweij, Niek
    Vonk, Judith M
    Waite, Lindsay L
    Waldenberger, Melanie
    Wennauer, Roman
    Wilkens, Lynne R
    Willenborg, Christina
    Wilsgaard, Tom
    Wojczynski, Mary K
    Wong, Andrew
    Wright, Alan F
    Zhang, Qunyuan
    Arveiler, Dominique
    Bakker, Stephan J L
    Beilby, John
    Bergman, Richard N
    Bergmann, Sven
    Biffar, Reiner
    Blangero, John
    Boomsma, Dorret I
    Bornstein, Stefan R
    Bovet, Pascal
    Brambilla, Paolo
    Brown, Morris J
    Campbell, Harry
    Caulfield, Mark J
    Chakravarti, Aravinda
    Collins, Rory
    Collins, Francis S
    Crawford, Dana C
    Cupples, L Adrienne
    Danesh, John
    de Faire, Ulf
    den Ruijter, Hester M
    Erbel, Raimund
    Erdmann, Jeanette
    Eriksson, Johan G
    Farrall, Martin
    Ferrannini, Ele
    Ferrières, Jean
    Ford, Ian
    Forouhi, Nita G
    Forrester, Terrence
    Gansevoort, Ron T
    Gejman, Pablo V
    Gieger, Christian
    Golay, Alain
    Gottesman, Omri
    Gudnason, Vilmundur
    Gyllensten, Ulf
    Haas, David W
    Hall, Alistair S
    Harris, Tamara B
    Hattersley, Andrew T
    Heath, Andrew C
    Hengstenberg, Christian
    Hicks, Andrew A
    Hindorff, Lucia A
    Hingorani, Aroon D
    Hofman, Albert
    Hovingh, G Kees
    Humphries, Steve E
    Hunt, Steven C
    Hypponen, Elina
    Jacobs, Kevin B
    Jarvelin, Marjo-Riitta
    Jousilahti, Pekka
    Jula, Antti M
    Kaprio, Jaakko
    Kastelein, John J P
    Kayser, Manfred
    Kee, Frank
    Keinanen-Kiukaanniemi, Sirkka M
    Kiemeney, Lambertus A
    Kooner, Jaspal S
    Kooperberg, Charles
    Koskinen, Seppo
    Kovacs, Peter
    Kraja, Aldi T
    Kumari, Meena
    Kuusisto, Johanna
    Lakka, Timo A
    Langenberg, Claudia
    Le Marchand, Loic
    Lehtimäki, Terho
    Lupoli, Sara
    Madden, Pamela A F
    Männistö, Satu
    Manunta, Paolo
    Marette, André
    Matise, Tara C
    McKnight, Barbara
    Meitinger, Thomas
    Moll, Frans L
    Montgomery, Grant W
    Morris, Andrew D
    Morris, Andrew P
    Murray, Jeffrey C
    Nelis, Mari
    Ohlsson, Claes
    Oldehinkel, Albertine J
    Ong, Ken K
    Ouwehand, Willem H
    Pasterkamp, Gerard
    Peters, Annette
    Pramstaller, Peter P
    Price, Jackie F
    Qi, Lu
    Raitakari, Olli T
    Rankinen, Tuomo
    Rao, D C
    Rice, Treva K
    Ritchie, Marylyn
    Rudan, Igor
    Salomaa, Veikko
    Samani, Nilesh J
    Saramies, Jouko
    Sarzynski, Mark A
    Schwarz, Peter E H
    Sebert, Sylvain
    Sever, Peter
    Shuldiner, Alan R
    Sinisalo, Juha
    Steinthorsdottir, Valgerdur
    Stolk, Ronald P
    Tardif, Jean-Claude
    Tönjes, Anke
    Tremblay, Angelo
    Tremoli, Elena
    Virtamo, Jarmo
    Vohl, Marie-Claude
    Amouyel, Philippe
    Asselbergs, Folkert W
    Assimes, Themistocles L
    Bochud, Murielle
    Boehm, Bernhard O
    Boerwinkle, Eric
    Bottinger, Erwin P
    Bouchard, Claude
    Cauchi, Stéphane
    Chambers, John C
    Chanock, Stephen J
    Cooper, Richard S
    de Bakker, Paul I W
    Dedoussis, George
    Ferrucci, Luigi
    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, Skåne University Hospital, Malmö, Sweden.
    Froguel, Philippe
    Groop, Leif C
    Haiman, Christopher A
    Hamsten, Anders
    Hayes, M Geoffrey
    Hui, Jennie
    Hunter, David J
    Hveem, Kristian
    Jukema, J Wouter
    Kaplan, Robert C
    Kivimaki, Mika
    Kuh, Diana
    Laakso, Markku
    Liu, Yongmei
    Martin, Nicholas G
    März, Winfried
    Melbye, Mads
    Moebus, Susanne
    Munroe, Patricia B
    Njølstad, Inger
    Oostra, Ben A
    Palmer, Colin N A
    Pedersen, Nancy L
    Perola, Markus
    Pérusse, Louis
    Peters, Ulrike
    Powell, Joseph E
    Power, Chris
    Quertermous, Thomas
    Rauramaa, Rainer
    Reinmaa, Eva
    Ridker, Paul M
    Rivadeneira, Fernando
    Rotter, Jerome I
    Saaristo, Timo E
    Saleheen, Danish
    Schlessinger, David
    Slagboom, P Eline
    Snieder, Harold
    Spector, Tim D
    Strauch, Konstantin
    Stumvoll, Michael
    Tuomilehto, Jaakko
    Uusitupa, Matti
    van der Harst, Pim
    Völzke, Henry
    Walker, Mark
    Wareham, Nicholas J
    Watkins, Hugh
    Wichmann, H-Erich
    Wilson, James F
    Zanen, Pieter
    Deloukas, Panos
    Heid, Iris M
    Lindgren, Cecilia M
    Mohlke, Karen L
    Speliotes, Elizabeth K
    Thorsteinsdottir, Unnur
    Barroso, Inês
    Fox, Caroline S
    North, Kari E
    Strachan, David P
    Beckmann, Jacques S
    Berndt, Sonja I
    Boehnke, Michael
    Borecki, Ingrid B
    McCarthy, Mark I
    Metspalu, Andres
    Stefansson, Kari
    Uitterlinden, André G
    van Duijn, Cornelia M
    Franke, Lude
    Willer, Cristen J
    Price, Alkes L
    Lettre, Guillaume
    Loos, Ruth J F
    Weedon, Michael N
    Ingelsson, Erik
    O'Connell, Jeffrey R
    Abecasis, Goncalo R
    Chasman, Daniel I
    Goddard, Michael E
    Visscher, Peter M
    Hirschhorn, Joel N
    Frayling, Timothy M
    Defining the role of common variation in the genomic and biological architecture of adult human height2014Ingår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 46, nr 11, s. 1173-1186Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

  • 239. Yates, Thomas
    et al.
    Zaccardi, Francesco
    Dhalwani, Nafeesa N.
    Davies, Melanie J.
    Bakrania, Kishan
    Celis-Morales, Carlos A.
    Gill, Jason M. R.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Khunti, Kamlesh
    Association of walking pace and handgrip strength with all-cause, cardiovascular, and cancer mortality: a UK Biobank observational study2017Ingår i: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 38, nr 43, s. 3232-3240Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    To quantify the association of self-reported walking pace and handgrip strength with all-cause, cardiovascular, and cancer mortality. A total of 230 670 women and 190 057 men free from prevalent cancer and cardiovascular disease were included from UK Biobank. Usual walking pace was self-defined as slow, steady/average or brisk. Handgrip strength was assessed by dynamometer. Cox-proportional hazard models were adjusted for social deprivation, ethnicity, employment, medications, alcohol use, diet, physical activity, and television viewing time. Interaction terms investigated whether age, body mass index (BMI), and smoking status modified associations. Over 6.3 years, there were 8598 deaths, 1654 from cardiovascular disease and 4850 from cancer. Associations of walking pace with mortality were modified by BMI. In women, the hazard ratio (HR) for all-cause mortality in slow compared with fast walkers were 2.16 [95% confidence interval (CI): 1.68-2.77] and 1.31 (1.08-1.60) in the bottom and top BMI tertiles, respectively; corresponding HRs for men were 2.01 (1.68-2.41) and 1.41 (1.20-1.66). Hazard ratios for cardiovascular mortality remained above 1.7 across all categories of BMI in men and women, with modest heterogeneity in men. Handgrip strength was associated with cardiovascular mortality in men only (HR tertile 1 vs. tertile 3 = 1.38; 1.18-1.62), without differences across BMI categories, while associations with all-cause mortality were only seen in men with low BMI. Associations for walking pace and handgrip strength with cancer mortality were less consistent. A simple self-reported measure of slow walking pace could aid risk stratification for all-cause and cardiovascular mortality within the general population.

  • 240. Zheng, Ju-Sheng
    et al.
    Sharp, Stephen J.
    Imamura, Fumiaki
    Koulman, Albert
    Schulze, Matthias B.
    Ye, Zheng
    Griffin, Jules
    Guevara, Marcela
    María Huerta, José
    Kröger, Janine
    Sluijs, Ivonne
    Agudo, Antonio
    Barricarte, Aurelio
    Boeing, Heiner
    Colorado-Yohar, Sandra
    Dow, Courtney
    Dorronsoro, Miren
    Dinesen, Pia T.
    Fagherazzi, Guy
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Lund University, Malmö, Sweden.
    Feskens, Edith J. M.
    Kühn, Tilman
    Katzke, Verena Andrea
    Key, Timothy J.
    Khaw, Kay-Tee
    de Magistris, Maria Santucci
    Romana Mancini, Francesca
    Molina-Portillo, Elena
    Nilsson, Peter M.
    Olsen, Anja
    Overvad, Kim
    Palli, Domenico
    Ramón Quirós, Jose
    Rolandsson, Olov
    Ricceri, Fulvio
    Spijkerman, Annemieke M. W.
    Slimani, Nadia
    Tagliabue, Giovanna
    Tjonneland, Anne
    Tumino, Rosario
    van der Schouw, Yvonne T.
    Langenberg, Claudia
    Riboli, Elio
    Forouhi, Nita G.
    Wareham, Nicholas J.
    Association between plasma phospholipid saturated fatty acids and metabolic markers of lipid, hepatic, inflammation and glycaemic pathways in eight European countries: a cross-sectional analysis in the EPIC-InterAct study2017Ingår i: BMC Medicine, ISSN 1741-7015, E-ISSN 1741-7015, Vol. 15, artikel-id 203Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Accumulating evidence suggests that individual circulating saturated fatty acids (SFAs) are heterogeneous in their associations with cardio-metabolic diseases, but evidence about associations of SFAs with metabolic markers of different pathogenic pathways is limited. We aimed to examine the associations between plasma phospholipid SFAs and the metabolic markers of lipid, hepatic, glycaemic and inflammation pathways. Methods: We measured nine individual plasma phospholipid SFAs and derived three SFA groups (odd-chain: C15:0 + C17:0, even-chain: C14:0 + C16:0 + C18:0, and very-long-chain: C20:0 + C22:0 + C23:0 + C24:0) in individuals from the subcohort of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study across eight European countries. Using linear regression in 15,919 subcohort members, adjusted for potential confounders and corrected for multiple testing, we examined cross-sectional associations of SFAs with 13 metabolic markers. Multiplicative interactions of the three SFA groups with pre-specified factors, including body mass index (BMI) and alcohol consumption, were tested. Results: Higher levels of odd-chain SFA group were associated with lower levels of major lipids (total cholesterol (TC), triglycerides, apolipoprotein A-1 (ApoA1), apolipoprotein B (ApoB)) and hepatic markers (alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT)). Higher even-chain SFA group levels were associated with higher levels of low-density lipoprotein cholesterol (LDL-C), TC/high-density lipoprotein cholesterol (HDL-C) ratio, triglycerides, ApoB, ApoB/A1 ratio, ALT, AST, GGT and CRP, and lower levels of HDL-C and ApoA1. Very-long-chain SFA group levels showed inverse associations with triglycerides, ApoA1 and GGT, and positive associations with TC, LDL-C, TC/HDL-C, ApoB and ApoB/A1. Associations were generally stronger at higher levels of BMI or alcohol consumption. Conclusions: Subtypes of SFAs are associated in a differential way with metabolic markers of lipid metabolism, liver function and chronic inflammation, suggesting that odd-chain SFAs are associated with lower metabolic risk and even-chain SFAs with adverse metabolic risk, whereas mixed findings were obtained for very-long-chain SFAs. The clinical and biochemical implications of these findings may vary by adiposity and alcohol intake.

  • 241.
    Zhou, Kaixin
    et al.
    Division of Cardiovascular & Diabetes Medicine, Medical Research Institute, University of Dundee, Dundee, U.K..
    Donnelly, Louise A.
    Division of Cardiovascular & Diabetes Medicine, Medical Research Institute, University of Dundee, Dundee, U.K..
    Morris, Andrew D.
    Division of Cardiovascular & Diabetes Medicine, Medical Research Institute, University of Dundee, Dundee, U.K..
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Clinical Science, Genetic & Molecular Epidemiology Unit, Lund University, Malmö, Sweden ; Department of Nutrition, Harvard University, School of Public Health, Boston, MA.
    Jennison, Chris
    Department of Mathematical Sciences, University of Bath, Bath, U.K..
    Palmer, Colin N. A.
    Division of Cardiovascular & Diabetes Medicine, Medical Research Institute, University of Dundee, Dundee, U.K..
    Pearson, Ewan R.
    Division of Cardiovascular & Diabetes Medicine, Medical Research Institute, University of Dundee, Dundee, U.K..
    Clinical and genetic determinants of progression of type 2 diabetes: a DIRECT study2014Ingår i: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 37, nr 3, s. 718-724Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To identify the clinical and genetic factors that explain why the rate of diabetes progression is highly variable between idividuals following diagnosis of type 2 diabetes.

    RESEARCH DESIGN AND METHODS: We studied 5,250 patients with type 2 diabetes using comprehensive electronic medical records in Tayside, Scotland, from 1992 onward. We investigated the association of clinical, biochemical, and genetic factors with the risk of progression of type 2 diabetes from diagnosis to the requirement of insulin treatment (defined as insulin treatment or HbA(1c) 8.5% [69 mmol/mol] treated with two or more noninsulin therapies).RESULTSRisk of progression was associated with both low and high BMI. In an analysis stratified by BMI and HbA(1c) at diagnosis, faster progression was independently associated with younger age at diagnosis, higher log triacylglyceride (TG) concentrations (hazard ratio [HR] 1.28 per mmol/L [95% CI 1.15-1.42]) and lower HDL concentrations (HR 0.70 per mmol/L [95% CI 0.55-0.87]). A high Genetic Risk Score derived from 61 diabetes risk variants was associated with a younger age at diagnosis and a younger age when starting insulin but was not associated with the progression rate from diabetes to the requirement of insulin treatment.

    CONCLUSIONS: Increased TG and low HDL levels are independently associated with increased rate of progression of diabetes. The genetic factors that predispose to diabetes are different from those that cause rapid progression of diabetes, suggesting a difference in biological process that needs further investigation.

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