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  • 101.
    Gradmark, Anna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Pomeroy, J
    Renström, Frida
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Steiginga, S
    Persson, M
    Wright, A
    Bluck, L
    Domellöf, M
    Kahn, SE
    Mogren, I
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Physical activity, sedentary behaviors, and estimated insulin sensitivity and secretion in pregnant and non-pregnant women2011Övrigt (Övrigt vetenskapligt)
    Abstract [en]

    Aims Overweight and obesity during pregnancy raise the risk of gestational diabetes and birth complications. Lifestyle factors such as physical activity may decrease these risks through beneficial effects on systemic glucose homeostasis. Here we examined physical activity patterns and their relationships with measures of glucose homeostasis in late pregnancy compared to non-pregnant women.

    Methods Normal weight and overweight women without diabetes (N=108; aged 25-35 years) were studied; 35 were pregnant (in gestational weeks 28-32) and 73 were non-pregnant. An oral glucose tolerance test was conducted from which insulin sensitivity and β-cell response were estimated. Physical activity was measured during 10-days of free-living using a combined heart rate sensor and accelerometer. Total (TEE), resting (REE), and physical activity (PAEE) energy expenditure were measured using doubly-labeled water and expired gas indirect calorimetry.

    Results Total activity (counts/day) was associated with a reduced first-phase insulin response in both pregnant (r=-0.47; 95% CI: -0.70- to -0.15) and non-pregnant women (r=-0.36; 95% CI: -0.56- to -0.12). Pregnant women were estimated to have secreted more insulin (p=0.002) and had lower fasting glucose than non-pregnant women (p<0.0001). Measures of overall

    physical activity intensity were similar in both groups (p=0.547), but pregnant women spent more time sedentary (p<0.0001), less time in moderate-to-vigorous intensity activity (p<0.0001), had lower objectively measured total activity, and had lower physical activity energy expenditure (PAEE) than non-pregnant women (p=0.045).

    Conclusions Our findings suggest that physical activity conveys similar benefits on glucose homeostasis in pregnant and non-pregnant women, despite differences in subcomponents of physical activity.

  • 102.
    Gradmark, Anna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Pomeroy, Jeremy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Renström, Frida
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Steiginga, Susanne
    Free University Medical Center, Amsterdam, the Netherlands.
    Persson, Margareta
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap.
    Wright, Antony
    MRC Human Nutrition Research, Cambridge, UK..
    Bluck, Les
    MRC Human Nutrition Research, Cambridge, UK..
    Domellöf, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Kahn, Steven E
    Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, VA Puget Sound Health Care System and University of Washington, Seattle, WA, USA .
    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.
    Physical activity, sedentary behaviors, and estimated insulin sensitivity and secretion in pregnant and non-pregnant women2011Ingår i: BMC Pregnancy and Childbirth, ISSN 1471-2393, E-ISSN 1471-2393, Vol. 11, nr 1, s. 44-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Overweight and obesity during pregnancy raise the risk of gestational diabetes and birth complications. Lifestyle factors like physical activity may decrease these risks through beneficial effects on glucose homeostasis. Here we examined physical activity patterns and their relationships with measures of glucose homeostasis in late pregnancy compared to non-pregnant women.

    Methods: Normal weight and overweight women without diabetes (N=108; aged 25-35 years) were studied; 35 were pregnant (in gestational weeks 28-32) and 73 were non-pregnant. Insulin sensitivity and beta-cell response were estimated from an oral glucose tolerance test. Physical activity was measured during 10-days of free-living using a combined heart rate sensor and accelerometer. Total (TEE), resting (REE), and physical activity (PAEE) energy expenditure were measured using doubly-labeled water and expired gas indirect calorimetry.

    Results: Total activity was associated with reduced first-phase insulin response in both pregnant (Regression r2=0.11; Spearman r=-0.47; p=0.007) and non-pregnant women (Regression r2=0.11; Spearman; r=-0.36; p=0.002). Relative to non-pregnant women, pregnant women were estimated to have secreted 67% more insulin and had 10% lower fasting glucose than non-pregnant women. Pregnant women spent 13% more time sedentary, 71% less time in moderate-to-vigorous intensity activity, had 44% lower objectively measured total activity,and 12% lower PAEE than non-pregnant women. Correlations did not differ significantly for any comparison between physical activity subcomponents and measures of insulin sensitivity or secretion.

    Conclusions: Our findings suggest that physical activity conveys similar benefits on glucose homeostasis in pregnant and non-pregnant women, despite differences in subcomponents of physical activity.

  • 103. Graff, Mariaelisa
    et al.
    Scott, Robert A.
    Justice, Anne E.
    Young, Kristin L.
    Feitosa, Mary F.
    Barata, Llilda
    Winkler, Thomas W.
    Chu, Audrey Y.
    Mahajan, Anubha
    Hadley, David
    Xue, Luting
    Workalemahu, Tsegaselassie
    Heard-Costa, Nancy L.
    den Hoed, Marcel
    Ahluwalia, Tarunveer S.
    Qi, Qibin
    Ngwa, Julius S.
    Renström, Frida
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Lund Univ, Genet & Mol Epidemiol Unit, Dept Clin Sci, Malmo, Sweden.
    Quaye, Lydia
    Eicher, John D.
    Hayes, James E.
    Cornelis, Marilyn
    Kutalik, Zoltan
    Lim, Elise
    Luan, Jian'an
    Huffman, Jennifer E.
    Zhang, Weihua
    Zhao, Wei
    Griffin, Paula J.
    Haller, Toomas
    Ahmad, Shafqat
    Marques-Vidal, Pedro M.
    Bien, Stephanie
    Yengo, Loic
    Teumer, Alexander
    Smith, Albert Vernon
    Kumari, Meena
    Harder, Marie Neergaard
    Justesen, Johanne Marie
    Kleber, Marcus E.
    Hollensted, Mette
    Lohman, Kurt
    Rivera, Natalia V.
    Whitfield, John B.
    Zhao, Jing Hua
    Stringham, Heather M.
    Lyytikainen, Leo-Pekka
    Huppertz, Charlotte
    Willemsen, Gonneke
    Peyrot, Wouter J.
    Wu, Ying
    Kristiansson, Kati
    Demirkan, Ayse
    Fornage, Myriam
    Hassinen, Maija
    Bielak, Lawrence F.
    Cadby, Gemma
    Tanaka, Toshiko
    Magl, Reedlk
    Van der Most, Peter J.
    Jackson, Anne U.
    Bragg-Gresham, Jennifer L.
    Vitart, Veronique
    Marten, Jonathan
    Navarro, Pau
    Bellis, Claire
    Pasko, Dorota
    Johansson, Asa
    Snitker, Soren
    Cheng, Yu-Ching
    Eriksson, Joel
    Lim, Unhee
    Aadahl, Mette
    Adair, Linda S.
    Amin, Najaf
    Balkau, Beverley
    Auvinen, Juha
    Beilby, John
    Bergman, Richard N.
    Bergmann, Sven
    Bertoni, Alain G.
    Blangero, John
    Bonnefond, Amelle
    Bonnycastle, Lori L.
    Borja, Judith B.
    Brage, Soren
    Busonero, Fabio
    Buyske, Steve
    Campbell, Harry
    Chines, Peter S.
    Collins, Francis S.
    Corre, Tanguy
    Smith, George Davey
    Delgado, Graciela E.
    Dueker, Nicole
    Doerr, Marcus
    Ebeling, Tapani
    Eiriksdottir, Gudny
    Esko, Tonu
    Faul, Jessica D.
    Fu, Mao
    Faerch, Kristine
    Gieger, Christian
    Glaeser, Sven
    Gong, Jian
    Gordon-Larsen, Penny
    Grallert, Harald
    Grammer, Tanja B.
    Grarup, Niels
    van Grootheest, Gerard
    Harald, Kennet
    Hastie, Nicholas D.
    Havulinna, Aki S.
    Hernandez, Dena
    Hindorff, Lucia
    Hocking, Lynne J.
    Holmens, Oddgeir L.
    Holzapfel, Christina
    Hottenga, Jouke Jan
    Huang, Jie
    Huang, Tao
    Hui, Jennie
    Huth, Cornelia
    Hutri-Kahonen, Nina
    James, Alan L.
    Jansson, John-Olov
    Jhun, Min A.
    Juonala, Markus
    Kinnunen, Leena
    Koistinen, Heikki A.
    Kolcic, Ivana
    Komulainen, Pirjo
    Kuusisto, Johanna
    Kvaloy, Kirsti
    Kahonen, Mika
    Lakka, Timo A.
    Launer, Lenore J.
    Lehne, Benjamin
    Lindgren, Cecilia M.
    Lorentzon, Mattias
    Luben, Robert
    Marre, Michel
    Milaneschi, Yuri
    Monda, Keri L.
    Montgomery, Grant W.
    De Moor, Marleen H. M.
    Mulas, Antonella
    Mueller-Nurasyid, Martina
    Musk, A. W.
    Mannikko, Reija
    Mannisto, Satu
    Narisu, Narisu
    Nauck, Matthias
    Nettleton, Jennifer A.
    Nolte, Ilja M.
    Oldehinkel, Albertine J.
    Olden, Matthias
    Ong, Ken K.
    Padmanabhan, Sandosh
    Paternoster, Lavinia
    Perez, Jeremiah
    Perola, Markus
    Peters, Annette
    Peters, Ulrike
    Peyser, Patricia A.
    Prokopenko, Inga
    Puolijoki, Hannu
    Raitakari, Olli T.
    Rankinen, Tuomo
    Rasmussen-Torvik, Laura J.
    Rawal, Rajesh
    Ridker, Paul M.
    Rose, Lynda M.
    Rudan, Igor
    Sarti, Cinzia
    Sarzynski, Mark A.
    Savonen, Kai
    Scott, William R.
    Sanna, Serena
    Shuldiner, Alan R.
    Sidney, Steve
    Silbernagel, Guenther
    Smith, Blair H.
    Smith, Jennifer A.
    Snieder, Harold
    Stancakova, Alena
    Sternfeld, Barbara
    Swift, Amy J.
    Tammelin, Tuija
    Tan, Sian-Tsung
    Thorand, Barbara
    Thuillier, Dorothee
    Vandenput, Liesbeth
    Vestergaard, Henrik
    van Vliet-Ostaptchouk, Jana V.
    Vohl, Marie-Claude
    Voelker, Uwe
    Waeber, Gerard
    Walker, Mark
    Wild, Sarah
    Wong, Andrew
    Wright, Alan F.
    Zillikens, M. Carola
    Zubair, Niha
    Haiman, Christopher A.
    Lemarchand, Loic
    Gyllensten, Ulf
    Ohlsson, Claes
    Hofman, Albert
    Rivadeneira, Fernando
    Uitterlinden, Andre G.
    Perusse, Louis
    Wilson, James F.
    Hayward, Caroline
    Polasek, Ozren
    Cucca, Francesco
    Hveem, Kristian
    Hartman, Catharina A.
    Toenjes, Anke
    Bandinelli, Stefania
    Palmer, Lyle J.
    Kardia, Sharon L. R.
    Rauramaa, Rainer
    Sorensen, Thorkild I. A.
    Tuomilehto, Jaakko
    Salomaa, Veikko
    Penninx, Brenda W. J. H.
    de Geus, Eco J. C.
    Boomsma, Dorret I.
    Lehtimaki, Terho
    Mangino, Massimo
    Laakso, Markku
    Bouchard, Claude
    Martin, Nicholas G.
    Kuh, Diana
    Liu, Yongmei
    Linneberg, Allan
    Maerz, Winfried
    Strauch, Konstantin
    Kivimaki, Mika
    Harris, Tamara B.
    Gudnason, Vilmundur
    Voelzke, Henry
    Qi, Lu
    Jarvelin, Marjo-Riitta
    Chambers, John C.
    Kooner, Jaspal S.
    Froguel, Philippe
    Kooperberg, Charles
    Vollenweider, Peter
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Hansen, Torben
    Pedersen, Oluf
    Metspalu, Andres
    Wareham, Nicholas J.
    Langenberg, Claudia
    Weir, David R.
    Porteous, David J.
    Boerwinkle, Eric
    Chasman, Daniel I.
    Abecasis, Goncalo R.
    Barroso, Ines
    McCarthy, Mark I.
    Frayling, Timothy M.
    O'Connell, Jeffrey R.
    van Duijn, Cornelia M.
    Boehnke, Michael
    Heid, Iris M.
    Mohlke, Karen L.
    Strachan, David P.
    Fox, Caroline S.
    Liu, Ching-Ti
    Hirschhorn, Joel N.
    Klein, Robert J.
    Johnson, Andrew D.
    Borecki, Ingrid B.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA ; Lund Univ, Genet & Mol Epidemiol Unit, Dept Clin Sci, Malmo, Sweden.
    North, Kari E.
    Cupples, L. Adrienne
    Loos, Ruth J. F.
    Kilpelainen, Tuomas O.
    Genome-wide physical activity interactions in adiposity. A meta-analysis of 200,452 adults2017Ingår i: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 13, nr 4, artikel-id e1006528Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by similar to 30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.

  • 104. Grøntved, Anders
    et al.
    Andersen, Lars B
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Verhage, Bas
    Wareham, Nicholas J
    Ekelund, Ulf
    Loos, Ruth J F
    Brage, Søren
    NOS3 variants, physical activity, and blood pressure in the European Youth Heart Study2011Ingår i: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 24, nr 4, s. 444-450Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The NOS3 Glu298Asp variant may associate with resting BP in adolescence but not in childhood, an effect that could be modified by PA.

  • 105. Grøntved, Anders
    et al.
    Koivula, Robert W
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Wennberg, Patrik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Østergaard, Lars
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Renström, Frida
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Skåne University Hospital Malmö, Malmö, Sweden.
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. 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.
    Bicycling to Work and Primordial Prevention of Cardiovascular Risk: A Cohort Study Among Swedish Men and Women2016Ingår i: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 5, nr 11, artikel-id e004413Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Bicycling to work may be a viable approach for achieving physical activity that provides cardiovascular health benefits. In this study we investigated the relationship of bicycling to work with incidence of obesity, hypertension, hypertriglyceridemia, and impaired glucose tolerance across a decade of follow-up in middle-aged men and women.

    METHODS AND RESULTS: We followed 23 732 Swedish men and women with a mean age of 43.5 years at baseline who attended a health examination twice during a 10-year period (1990-2011). In multivariable adjusted models we calculated the odds of incident obesity, hypertension, hypertriglyceridemia, and impaired glucose tolerance, comparing individuals who commuted to work by bicycle with those who used passive modes of transportation. We also examined the relationship of change in commuting mode with incidence of these clinical risk factors. Cycling to work at baseline was associated with lower odds of incident obesity (odds ratio [OR]=0.85, 95% CI 0.73-0.99), hypertension (OR=0.87, 95% CI 0.79-0.95), hypertriglyceridemia (OR=0.85, 95% CI 0.76-0.94), and impaired glucose tolerance (OR=0.88, 95% CI 0.80-0.96) compared with passive travel after adjusting for putative confounding factors. Participants who maintained or began bicycling to work during follow-up had lower odds of obesity (OR=0.61, 95% CI 0.50-0.73), hypertension (OR=0.89, 95% CI 0.80-0.98), hypertriglyceridemia (OR=0.80, 95% CI 0.70-0.90), and impaired glucose tolerance (OR=0.82, 95% CI 0.74-0.91) compared with participants not cycling to work at both times points or who switched from cycling to other modes of transport during follow-up.

    CONCLUSIONS: These data suggest that commuting by bicycle to work is an important strategy for primordial prevention of clinical cardiovascular risk factors among middle-aged men and women.

  • 106. Guo, Yan
    et al.
    Ma, Lijun
    Enriori, Pablo J
    Koska, Juraj
    Franks, Paul
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Brookshire, Thomas
    Cowley, Michael A
    Salbe, Arline D
    Delparigi, Angelo
    Tataranni, P Antonio
    Physiological evidence for the involvement of peptide YY in the regulation of energy homeostasis in humans.2006Ingår i: Obesity (Silver Spring), ISSN 1930-7381, Vol. 14, nr 9, s. 1562-70Artikel i tidskrift (Refereegranskat)
  • 107. Haworth, Simon
    et al.
    Shungin, Dmitry
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Kwak, So Young
    Kim, Hae-Young
    West, Nicola X.
    Thomas, Steven J.
    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 Malmo, Malmö, Sweden; Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
    Timpson, Nicholas J.
    Shin, Min-Jeong
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Tooth loss is a complex measure of oral disease: determinants and methodological considerations2018Ingår i: Community Dentistry and Oral Epidemiology, ISSN 0301-5661, E-ISSN 1600-0528, Vol. 46, nr 6, s. 555-562Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: Counts of missing teeth or measures of incident tooth loss are gaining attention as a simple way to measure dental status in large population studies. We explore the meaning of these metrics and how missing teeth might influence other measures of dental status.

    METHODS: An observational study was performed in 2 contrasting adult populations. In total, 62 522 adult participants were available with clinically assessed caries and periodontal indices from the Swedish arm of the Gene-Lifestyle Interactions and Dental Endpoints Study (GLIDE) and the Korea National Health and Nutrition Examination Survey (KNHANES) in the Republic of Korea. Longitudinal measures of tooth loss were available for 28 244 participants in GLIDE with median follow-up of 10.6 years.

    RESULTS: In longitudinal analysis, hazard for tooth loss was associated with baseline dental status (previous tooth loss, periodontal status and caries status) and socio-demographic variables (age, smoking status and highest educational level). Analysis of cross-sectional data suggested that indices of caries exposure were not independent of periodontal status. The strength and direction of association varied between groups, even for measures specifically intended to avoid measuring tooth loss. Individuals with impaired periodontal health (community periodontal index [CPI] 3 or higher in any sextant) had higher standardized decayed and filled surfaces (DFS; number of DFS divided by total number of tooth surfaces) in GLIDE (incidence risk ratio [IRR] 1.05 [95% CI: 1.04, 1.07], but lower standardized DFS in KNHANES (IRR: 0.95 [0.92, 0.98]) than individuals with better periodontal health (CPI <3 in all sextants).

    CONCLUSIONS: Incident tooth loss is a complex measure of dental disease, with multiple determinants. The relative importance of dental caries and periodontal disease as drivers of tooth loss differs between age groups. Measures of dental caries exposure are associated with periodontal status in the studied populations, and these associations can be population-specific. Consideration of the study-specific properties of these metrics may be required for valid inference in large population studies.

  • 108. Haworth, Simon
    et al.
    Shungin, Dmitry
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi. Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142, USA.
    van der Tas, Justin T
    Vucic, Strahinja
    Medina-Gomez, Carolina
    Yakimov, Victor
    Feenstra, Bjarke
    Shaffer, John R
    Lee, Myoung Keun
    Standl, Marie
    Thiering, Elisabeth
    Wang, Carol
    Bønnelykke, Klaus
    Waage, Johannes
    Jessen, Leon Eyrich
    Nørrisgaard, Pia Elisabeth
    Joro, Raimo
    Seppälä, Ilkka
    Raitakari, Olli
    Dudding, Tom
    Grgic, Olja
    Ongkosuwito, Edwin
    Vierola, Anu
    Eloranta, Aino-Maija
    West, Nicola X
    Thomas, Steven J
    McNeil, Daniel W
    Levy, Steven M
    Slayton, Rebecca
    Nohr, Ellen A
    Lehtimäki, Terho
    Lakka, Timo
    Bisgaard, Hans
    Pennell, Craig
    Kühnisch, Jan
    Marazita, Mary L
    Melbye, Mads
    Geller, Frank
    Rivadeneira, Fernando
    Wolvius, Eppo B
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö 202 13, Sweden; Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Timpson, Nicholas J
    Consortium-based genome-wide meta-analysis for childhood dental caries traits2018Ingår i: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 27, nr 17, s. 3113-3127Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Prior studies suggest dental caries traits in children and adolescents are partially heritable, but there has been no large-scale consortium genome-wide association study (GWAS) to date. We therefore performed GWAS for caries in participants aged 2.5-18.0 years from nine contributing centres. Phenotype definitions were created for the presence or absence of treated or untreated caries, stratified by primary and permanent dentition. All studies tested for association between caries and genotype dosage and the results were combined using fixed-effects meta-analysis. Analysis included up to 19 003 individuals (7530 affected) for primary teeth and 13 353 individuals (5875 affected) for permanent teeth. Evidence for association with caries status was observed at rs1594318-C for primary teeth [intronic within ALLC, odds ratio (OR) 0.85, effect allele frequency (EAF) 0.60, P 4.13e-8] and rs7738851-A (intronic within NEDD9, OR 1.28, EAF 0.85, P 1.63e-8) for permanent teeth. Consortium-wide estimated heritability of caries was low [h2 of 1% (95% CI: 0%: 7%) and 6% (95% CI 0%: 13%) for primary and permanent dentitions, respectively] compared with corresponding within-study estimates [h2 of 28% (95% CI: 9%: 48%) and 17% (95% CI: 2%: 31%)] or previously published estimates. This study was designed to identify common genetic variants with modest effects which are consistent across different populations. We found few single variants associated with caries status under these assumptions. Phenotypic heterogeneity between cohorts and limited statistical power will have contributed; these findings could also reflect complexity not captured by our study design, such as genetic effects which are conditional on environmental exposure.

  • 109. He, Meian
    et al.
    Cornelis, Marilyn C
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Zhang, Cuilin
    Hu, Frank B
    Qi, Lu
    Obesity genotype score and cardiovascular risk in women with type 2 diabetes mellitus2010Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 30, nr 2, s. 327-332Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Obesity-predisposing variants may jointly affect CVD risk among women with diabetes.

  • 110. Hivert, Marie-France
    et al.
    Christophi, Costas A.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Jablonski, Kathleen A.
    Ehrmann, David A.
    Kahn, Steven E.
    Horton, Edward S.
    Pollin, Toni I.
    Mather, Kieren J.
    Perreault, Leigh
    Barrett-Connor, Elizabeth
    Knowler, William C.
    Florez, Jose C.
    Lifestyle and Metformin Ameliorate Insulin Sensitivity Independently of the Genetic Burden of Established Insulin Resistance Variants in Diabetes Prevention Program Participants2016Ingår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 65, nr 2, s. 520-526Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Large genome-wide association studies of glycemic traits have identified genetics variants that are associated with insulin resistance (IR) in the general population. It is unknown whether people with genetic enrichment for these IR variants respond differently to interventions that aim to improve insulin sensitivity. We built a genetic risk score (GRS) based on 17 established IR variants and effect sizes (weighted IR-GRS) in 2,713 participants of the Diabetes Prevention Program (DPP) with genetic consent. We tested associations between the weighted IR-GRS and insulin sensitivity index (ISI) at baseline in all participants, and with change in ISI over 1 year of follow-up in the DPP intervention (metformin and lifestyle) and control (placebo) arms. All models were adjusted for age, sex, ethnicity, and waist circumference at baseline (plus baseline ISI for 1-year ISI change models). A higher IR-GRS was associated with lower baseline ISI (beta= -0.754 [SE = 0.229] log-ISI per unit, P = 0.001 in fully adjusted models). There was no differential effect of treatment for the association between the IR-GRS on the change in ISI; higher IR-GRS was associated with an attenuation in ISI improvement over 1 year (beta = -0.520 [SE = 0.233], P = 0.03 in fully adjusted models; all treatment arms). Lifestyle intervention and metformin treatment improved the ISI, regardless of the genetic burden of IR variants.

  • 111. Hivert, Marie-France
    et al.
    Jablonski, Kathleen A
    Perreault, Leigh
    Saxena, Richa
    McAteer, Jarred B
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Hamman, Richard F
    Kahn, Steven E
    Haffner, Steven
    Meigs, James B
    Altshuler, David
    Knowler, William C
    Florez, Jose C
    Updated genetic score based on 34 confirmed type 2 diabetes Loci is associated with diabetes incidence and regression to normoglycemia in the diabetes prevention program2011Ingår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 60, nr 4, s. 1340-1348Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A high GRS is associated with increased risk of developing diabetes and lower probability of returning to NGR in high-risk individuals, but a lifestyle intervention attenuates this risk.

  • 112. Hruby, Adela
    et al.
    Ngwa, Julius S.
    Renström, Frida
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Wojczynski, Mary K.
    Ganna, Andrea
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Houston, Denise K.
    Jacques, Paul F.
    Kanoni, Stavroula
    Lehtimaki, Terho
    Lemaitre, Rozenn N.
    Manichaikul, Ani
    North, Kari E.
    Ntalla, Ioanna
    Sonestedt, Emily
    Tanaka, Toshiko
    van Rooij, Frank J. A.
    Bandinelli, Stefania
    Djousse, Luc
    Grigoriou, Efi.
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Tandläkarutbildning.
    Lohman, Kurt K.
    Pankow, James S.
    Raitakari, Olli T.
    Riserus, Ulf
    Yannakoulia, Mary
    Zillikens, M. Carola
    Hassanali, Neelam
    Liu, Yongmei
    Mozaffarian, Dariush
    Papoutsakis, Constantina
    Syvanen, Ann-Christine
    Uitterlinden, Andre G.
    Viikari, Jorma
    Groves, Christopher J.
    Hofman, Albert
    Lind, Lars
    McCarthy, Mark I.
    Mikkila, Vera
    Mukamal, Kenneth
    Franco, Oscar H.
    Borecki, Ingrid B.
    Cupples, L. Adrienne
    Dedoussis, George V.
    Ferrucci, Luigi
    Hu, Frank B.
    Ingelsson, Erik
    Kahonen, Mika
    Kao, W. H. Linda
    Kritchevsky, Stephen B.
    Orho-Melander, Marju
    Prokopenko, Inga
    Rotter, Jerome I.
    Siscovick, David S.
    Witteman, Jacqueline C. M.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Meigs, James B.
    McKeown, Nicola M.
    Nettleton, Jennifer A.
    Higher Magnesium Intake Is Associated with Lower Fasting Glucose and Insulin, with No Evidence of Interaction with Select Genetic Loci, in a Meta-Analysis of 15 CHARGE Consortium Studies2013Ingår i: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 143, nr 3, s. 345-353Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Favorable associations between magnesium intake and glycemic traits, such as fasting glucose and insulin, are observed in observational and clinical studies, but whether genetic variation affects these associations is largely unknown. We hypothesized that single nucleotide polymorphisms (SNPs) associated with either glycemic traits or magnesium metabolism affect the association between magnesium intake and fasting glucose and insulin. Fifteen studies from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium provided data from up to 52,684 participants of European descent without known diabetes. In fixed-effects meta-analyses, we quantified 1) cross-sectional associations of dietary magnesium intake with fasting glucose (mmol/L) and insulin (In-pmol/L) and 2) interactions between magnesium intake and SNPs related to fasting glucose (16 SNPs), insulin (2 SNPs), or magnesium (8 SNPs) on fasting glucose and insulin. After adjustment for age, sex, energy intake, BMI, and behavioral risk factors, magnesium (per 50-mg/d increment) was inversely associated with fasting glucose [beta = -0.009 mmol/L (95% CI: -0.013, -0.005), P< 0.0001] and insulin (-0.020 In-pmo/L (95% CI: -0.024, -0.017), P< 0.0001]. No magnesium-related SNP or interaction between any SNP and magnesium reached significance after correction for multiple testing. However, rs2274924 in magnesium transporter-encoding TRPM6 showed a nominal association (uncorrected P= 0.03) with glucose, and rs11558471 in SLC30A8and rs3740393 near CNNM2showed a nominal interaction (uncorrected, both P = 0.02) with magnesium on glucose. Consistent with other studies, a higher magnesium intake was associated with lower fasting glucose and insulin. Nominal evidence of TRPM6 influence and magnesium interaction with select loci suggests that further investigation is warranted. J. Nutr. 143: 345-353, 2013.

  • 113. Huang, Tao
    et al.
    Ding, Ming
    Bergholdt, Helle K. M.
    Wang, Tiange
    Heianza, Yoriko
    Sun, Dian-jianyi
    Frazier-Wood, Alexis C.
    Aslibekyan, Stella
    North, Kari E.
    Voortman, Trudy
    Graff, Mariaelisa
    Smith, Caren E.
    Lai, Chao-Qiang
    Varbo, Anette
    Lemaitre, Rozenn N.
    de Jonge, M. Ester A. L.
    Fumeron, Fredric
    Corella, Dolores
    Wang, Carol A.
    Tjonneland, Anne
    Overvad, Kim
    Sorensen, Thorkild I. A.
    Feitosa, Mary F.
    Wojczynski, Mary K.
    Kahonen, Mika
    Renström, Frida
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Psaty, Bruce M.
    Siscovick, David S.
    Barroso, Ines
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Hernandez, Dena
    Ferrucci, Luigi
    Bandinelli, Stefania
    Linneberg, Allan
    Zillikens, M. Carola
    Sandholt, Camilla Helene
    Pedersen, Oluf
    Hansen, Torben
    Schulz, Christina-Alexandra
    Sonestedt, Emily
    Orho-Melander, Marju
    Chen, Tzu-An
    Rotter, Jerome I.
    Allison, Mathew A.
    Rich, Stephen S.
    Sorli, Jose V.
    Coltell, Oscar
    Pennell, Craig E.
    Eastwood, Peter
    Hofman, Albert
    Uitterlinden, Andre G.
    van Rooij, Frank J. A.
    Chu, Audrey Y.
    Rose, Lynda M.
    Ridker, Paul M.
    Viikari, Jorma
    Raitakari, Olli
    Lehtimaki, Terho
    Mikkila, Vera
    Willett, Walter C.
    Wang, Yujie
    Tucker, Katherine L.
    Ordovas, Jose M.
    Kilpelainen, Tuomas O.
    Province, Michael A.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Nutrition, Harvard School of Public Health, Boston, MA; Genetic and Molecular Epidemiology Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Arnett, Donna K.
    Tanaka, Toshiko
    Toft, Ulla
    Ericson, Ulrika
    Franco, Oscar H.
    Mozaffarian, Dariush
    Hu, Frank B.
    Chasman, Daniel I.
    Nordestgaard, Borge G.
    Ellervik, Christina
    Qi, Lu
    Dairy Consumption and Body Mass Index Among Adults: Mendelian Randomization Analysis of 184802 Individuals from 25 Studies2018Ingår i: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 64, nr 1, s. 183-191Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Associations between dairy intake and body mass index (BMI) have been inconsistently observed in epidemiological studies, and the causal relationship remains ill defined.

    METHODS: We performed Mendelian randomization (MR) analysis using an established dairy intake-associated genetic polymorphism located upstream of the lactase gene (LCT-13910 C/T, rs4988235) as an instrumental variable (IV). Linear regression models were fitted to analyze associations between (a) dairy intake and BMI, (b) rs4988235 and dairy intake, and (c) rs4988235 and BMI in each study. The causal effect of dairy intake on BMI was quantified by IV estimators among 184802 participants from 25 studies.

    RESULTS: Higher dairy intake was associated with higher BMI (β = 0.03 kg/m2 per serving/day; 95% CI, 0.00–0.06; P = 0.04), whereas the LCT genotype with 1 or 2 T allele was significantly associated with 0.20 (95% CI, 0.14–0.25) serving/day higher dairy intake (P = 3.15 × 10−12) and 0.12 (95% CI, 0.06–0.17) kg/m2 higher BMI (P = 2.11 × 10−5). MR analysis showed that the genetically determined higher dairy intake was significantly associated with higher BMI (β = 0.60 kg/m2 per serving/day; 95% CI, 0.27–0.92; P = 3.0 × 10−4).

    CONCLUSIONS: The present study provides strong evidence to support a causal effect of higher dairy intake on increased BMI among adults.

  • 114. Huang, Terry T-K
    et al.
    Ball, Geoff D C
    Franks, Paul
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Metabolic syndrome in youth: current issues and challenges.2007Ingår i: Appl Physiol Nutr Metab, ISSN 1715-5312, Vol. 32, nr 1, s. 13-22Artikel i tidskrift (Refereegranskat)
  • 115. Imamura, Fumiaki
    et al.
    Schulze, Matthias B
    Sharp, Stephen J
    Guevara, Marcela
    Romaguera, Dora
    Bendinelli, Benedetta
    Salamanca-Fernández, Elena
    Ardanaz, Eva
    Arriola, Larraitz
    Aune, Dagfinn
    Boeing, Heiner
    Dow, Courtney
    Fagherazzi, Guy
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin. Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden.
    Freisling, Heinz
    Jakszyn, Paula
    Kaaks, Rudolf
    Khaw, Kay-Tee
    Kühn, Tilman
    Mancini, Francesca R
    Masala, Giovanna
    Chirlaque, Maria-Dolores
    Nilsson, Peter M
    Overvad, Kim
    Pala, Valeria M
    Panico, Salvatore
    Perez-Cornago, Aurora
    Quirós, Jose R
    Ricceri, Fulvio
    Rodríguez-Barranco, Miguel
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Sluijs, Ivonne
    Stepien, Magdalena
    Spijkerman, Annemieke M W
    Tjønneland, Anne
    Tong, Tammy Y N
    Tumino, Rosario
    Vissers, Linda E T
    Ward, Heather A
    Langenberg, Claudia
    Riboli, Elio
    Forouhi, Nita G
    Wareham, Nick J
    Estimated Substitution of Tea or Coffee for Sugar-Sweetened Beverages Was Associated with Lower Type 2 Diabetes Incidence in Case–Cohort Analysis across 8 European Countries in the EPIC-InterAct Study2019Ingår i: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Beverage consumption is a modifiable risk factor for type 2 diabetes (T2D), but there is insufficient evidence to inform the suitability of substituting 1 type of beverage for another.

    Objective: The aim of this study was to estimate the risk of T2D when consumption of sugar-sweetened beverages (SSBs) was replaced with consumption of fruit juice, milk, coffee, or tea.

    Methods: In the European Prospective Investigation into Cancer and Nutrition (EPIC)–InterAct case–cohort study of 8 European countries (= 27,662, with 12,333 cases of incident T2D, 1992–2007), beverage consumption was estimated at baseline by dietary questionnaires. Using Prentice-weighted Cox regression adjusting for other beverages and potential confounders, we estimated associations of substituting 1 type of beverage for another on incident T2D.

    Results: Mean ± SD of estimated consumption of SSB was 55 ± 105 g/d. Means ± SDs for the other beverages were as follows: fruit juice, 59 ± 101 g/d; milk, 209 ± 203 g/d; coffee, 381 ± 372 g/d; and tea, 152 ± 282 g/d. Substituting coffee for SSBs by 250 g/d was associated with a 21% lower incidence of T2D (95% CI: 12%, 29%). The rate difference was −12.0 (95% CI: −20.0, −5.0) per 10,000 person-years among adults consuming SSBs ≥250 g/d (absolute rate = 48.3/10,000). Substituting tea for SSBs was estimated to lower T2D incidence by 22% (95% CI: 15%, 28%) or −11.0 (95% CI: −20.0, −2.6) per 10,000 person-years, whereas substituting fruit juice or milk was estimated not to alter T2D risk significantly.

    Conclusions: These findings indicate a potential benefit of substituting coffee or tea for SSBs for the primary prevention of T2D and may help formulate public health recommendations on beverage consumption in different populations.

  • 116. Imamura, Fumiaki
    et al.
    Sharp, Stephen J.
    Koulman, Albert
    Schulze, Matthias B.
    Kröger, Janine
    Griffin, Julian L.
    Huerta, José M.
    Guevara, Marcela
    Sluijs, Ivonne
    Agudo, Antonio
    Ardanaz, Eva
    Balkau, Beverley
    Boeing, Heiner
    Chajes, Veronique
    Dahm, Christina C.
    Dow, Courtney
    Fagherazzi, Guy
    Feskens, Edith J. M.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin. Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden.
    Gavrila, Diana
    Gunter, Marc
    Kaaks, Rudolf
    Key, Timothy J.
    Khaw, Kay-Tee
    Kuehn, Tilman
    Melander, Olle
    Molina-Portillo, Elena
    Nilsson, Peter M.
    Olsen, Anja
    Overvad, Kim
    Palli, Domenico
    Panico, Salvatore
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Sieri, Sabina
    Sacerdote, Carlotta
    Slimani, Nadia
    Spijkerman, Annemieke M. W.
    Tjønneland, Anne
    Tumino, Rosario
    van der Schouw, Yvonne T.
    Langenberg, Claudia
    Riboli, Elio
    Forouhi, Nita G.
    Wareham, Nick J.
    A combination of plasma phospholipid fatty acids and its association with incidence of type 2 diabetes: The EPIC-InterAct case-cohort study2017Ingår i: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 14, nr 10, artikel-id e1002409Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Combinations of multiple fatty acids may influence cardiometabolic risk more than single fatty acids. The association of a combination of fatty acids with incident type 2 diabetes (T2D) has not been evaluated.

    Methods and findings We measured plasma phospholipid fatty acids by gas chromatography in 27,296 adults, including 12,132 incident cases of T2D, over the follow-up period between baseline (1991-1998) and 31 December 2007 in 8 European countries in EPIC-InterAct, a nested casecohort study. The first principal component derived by principal component analysis of 27 individual fatty acids (mole percentage) was the main exposure (subsequently called the fatty acid pattern score [FA-pattern score]). The FA-pattern score was partly characterised by high concentrations of linoleic acid, stearic acid, odd-chain fatty acids, and very-long-chain saturated fatty acids and low concentrations of.-linolenic acid, palmitic acid, and long-chain monounsaturated fatty acids, and it explained 16.1% of the overall variability of the 27 fatty acids. Based on country-specific Prentice-weighted Cox regression and random-effects meta-analysis, the FA-pattern score was associated with lower incident T2D. Comparing the top to the bottom fifth of the score, the hazard ratio of incident T2D was 0.23 (95% CI 0.19-0.29) adjusted for potential confounders and 0.37 (95% CI 0.27-0.50) further adjusted for metabolic risk factors. The association changed little after adjustment for individual fatty acids or fatty acid subclasses. In cross-sectional analyses relating the FA-pattern score to metabolic, genetic, and dietary factors, the FA-pattern score was inversely associated with adiposity, triglycerides, liver enzymes, C-reactive protein, a genetic score representing insulin resistance, and dietary intakes of soft drinks and alcohol and was positively associated with high-density-lipoprotein cholesterol and intakes of polyunsaturated fat, dietary fibre, and coffee (p < 0.05 each). Limitations include potential measurement error in the fatty acids and other model covariates and possible residual confounding.

    Conclusions A combination of individual fatty acids, characterised by high concentrations of linoleic acid, odd-chain fatty acids, and very long-chain fatty acids, was associated with lower incidence of T2D. The specific fatty acid pattern may be influenced by metabolic, genetic, and dietary factors.

  • 117. Jablonski, Kathleen A
    et al.
    McAteer, Jarred B
    de Bakker, Paul I W
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Pollin, Toni I
    Hanson, Robert L
    Saxena, Richa
    Fowler, Sarah
    Shuldiner, Alan R
    Knowler, William C
    Altshuler, David
    Florez, Jose C
    Common variants in 40 genes assessed for diabetes incidence and response to metformin and lifestyle intervention in the diabetes prevention program2010Ingår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 59, nr 10, s. 2672-2681Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We have identified potential genetic determinants of metformin response. These results merit confirmation in independent samples.

  • 118. Jakobsdottir, Johanna
    et al.
    van der Lee, Sven J.
    Bis, Joshua C.
    Chouraki, Vincent
    Li-Kroeger, David
    Yamamoto, Shinya
    Grove, Megan L.
    Naj, Adam
    Vronskaya, Maria
    Salazar, Jose L.
    DeStefano, Anita L.
    Brody, Jennifer A.
    Smith, Albert V.
    Amin, Najaf
    Sims, Rebecca
    Ibrahim-Verbaas, Carla A.
    Choi, Seung-Hoan
    Satizabal, Claudia L.
    Lopez, Oscar L.
    Beiser, Alexa
    Ikram, M. Arfan
    Garcia, Melissa E.
    Hayward, Caroline
    Varga, Tibor V.
    Ripatti, Samuli
    Franks, Paul W.
    Department of Public Health & Clinical Medicine, Umeå University Hospital, Umeå, Sweden; .
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Jansson, Jan-Hakon
    Porteous, David J.
    Salomaa, Veikko
    Eiriksdottir, Gudny
    Rice, Kenneth M.
    Bellen, Hugo J.
    Levy, Daniel
    Uitterlinden, Andre G.
    Emilsson, Valur
    Rotter, Jerome I.
    Aspelund, Thor
    O'Donnell, Christopher J.
    Fitzpatrick, Annette L.
    Launer, Lenore J.
    Hofman, Albert
    Wang, Li-San
    Williams, Julie
    Schellenberg, Gerard D.
    Boerwinkle, Eric
    Psaty, Bruce M.
    Seshadri, Sudha
    Shulman, Joshua M.
    Gudnason, Vilmundur
    Van Duijn, Cornelia M.
    Rare Functional Variant in TM2D3 is Associated with Late-Onset Alzheimer's Disease2016Ingår i: PLoS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 12, nr 10, artikel-id e1006327Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We performed an exome-wide association analysis in 1393 late-onset Alzheimer's disease (LOAD) cases and 8141 controls from the CHARGE consortium. We found that a rare variant (P155L) in TM2D3 was enriched in Icelanders (similar to 0.5% versus < 0.05% in other European populations). In 433 LOAD cases and 3903 controls from the Icelandic AGES substudy, P155L was associated with increased risk and earlier onset of LOAD [odds ratio (95% CI) = 7.5 (3.5-15.9), p = 6.6x10(-9)]. Mutation in the Drosophila TM2D3 homolog, almondex, causes a phenotype similar to loss of Notch/Presenilin signaling. Human TM2D3 is capable of rescuing these phenotypes, but this activity is abolished by P155L, establishing it as a functionally damaging allele. Our results establish a rare TM2D3 variant in association with LOAD susceptibility, and together with prior work suggests possible links to the beta-amyloid cascade.

  • 119. Jannasch, Franziska
    et al.
    Kroeger, Janine
    Agnoli, Claudia
    Barricarte, Aurelio
    Boeing, Heiner
    Cayssials, Valerie
    Colorado-Yohar, Sandra
    Dahm, Christina C.
    Dow, Courtney
    Fagherazzi, Guy
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin. Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Freisling, Heinz
    Gunter, Marc J.
    Kerrison, Nicola D.
    Key, Timothy J.
    Khaw, Kay-Tee
    Kuehn, Tilman
    Kyro, Cecilie
    Mancini, Francesca Romana
    Mokoroa, Olatz
    Nilsson, Peter
    Overvad, Kim
    Palli, Domenico
    Panico, Salvatore
    Quiros Garcia, Jose Ramon
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Sacerdote, Carlotta
    Sanchez, Maria-Jose
    Sahrai, Mohammad Sediq
    Schuebel, Ruth
    Sluijs, Ivonne
    Spijkerman, Annemieke M. W.
    Tjonneland, Anne
    Tong, Tammy Y. N.
    Tumino, Rosario
    Riboli, Elio
    Langenberg, Claudia
    Sharp, Stephen J.
    Forouhi, Nita G.
    Schulze, Matthias B.
    Wareham, Nicholas J.
    Generalizability of a Diabetes-Associated Country-Specific Exploratory Dietary Pattern Is Feasible Across European Populations2019Ingår i: Journal of Nutrition, ISSN 0022-3166, E-ISSN 1541-6100, Vol. 149, nr 6, s. 1047-1055Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Population-specificity of exploratory dietary patterns limits their generalizability in investigations with type 2 diabetes incidence.

    Objective: The aim of this study was to derive country-specific exploratory dietary patterns, investigate their association with type 2 diabetes incidence, and replicate diabetes-associated dietary patterns in other countries.

    Methods: Dietary intake data were used, assessed by country-specific questionnaires at baseline of 11,183 incident diabetes cases and 14,694 subcohort members (mean age 52.9 y) from 8 countries, nested within the European Prospective Investigation into Cancer and Nutrition study (mean follow-up time 6.9 y). Exploratory dietary patterns were derived by principal component analysis. HRs for incident type 2 diabetes were calculated by Prentice-weighted Cox proportional hazard regression models. Diabetes-associated dietary patterns were simplified or replicated to be applicable in other countries. A meta-analysis across all countries evaluated the generalizability of the diabetes-association.

    Results: Two dietary patterns per country/UK-center, of which overall 3 dietary patterns were diabetes-associated, were identified. A risk-lowering French dietary pattern was not confirmed across other countries: pooled HRFrance per 1 SD: 1.00; 95% CI: 0.90, 1.10. Risk-increasing dietary patterns, derived in Spain and UK-Norfolk, were confirmed, but only the latter statistically significantly: HRSpain: 1.09; 95% CI: 0.97, 1.22 and HRUK-Norfolk: 1.12; 95% CI: 1.04, 1.20. Respectively, this dietary pattern was characterized by relatively high intakes of potatoes, processed meat, vegetable oils, sugar, cake and cookies, and tea.

    Conclusions: Only few country/center-specific dietary patterns (3 of 18) were statistically significantly associated with diabetes incidence in this multicountry European study population. One pattern, whose association with diabetes was confirmed across other countries, showed overlaps in the food groups potatoes and processed meat with identified diabetes-associated dietary patterns from other studies. The study demonstrates that replication of associations of exploratory patterns with health outcomes is feasible and a necessary step to overcome population-specificity in associations from such analyses.

  • 120. Ji, Yingjie
    et al.
    Yiorkas, Andrianos M.
    Frau, Francesca
    Mook-Kanamori, Dennis
    Staiger, Harald
    Thomas, E. Louise
    Atabaki-Pasdar, Naeimeh
    Campbell, Archie
    Tyrrell, Jessica
    Jones, Samuel E.
    Beaumont, Robin N.
    Wood, Andrew R.
    Tuke, Marcus A.
    Ruth, Katherine S.
    Mahajan, Anubha
    Murray, Anna
    Freathy, Rachel M.
    Weedon, Michael N.
    Hattersley, Andrew T.
    Hayward, Caroline
    Machann, Juergen
    Haering, Hans-Ulrich
    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, MA.
    de Mutsert, Renee
    Pearson, Ewan
    Stefan, Norbert
    Frayling, Timothy M.
    Allebrandt, Karla V.
    Bell, Jimmy D.
    Blakemore, Alexandra I.
    Yaghootkar, Hanieh
    Genome-Wide and Abdominal MRI Data Provide Evidence That a Genetically Determined Favorable Adiposity Phenotype Is Characterized by Lower Ectopic Liver Fat and Lower Risk of Type 2 Diabetes, Heart Disease, and Hypertension2019Ingår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 68, nr 1, s. 207-219Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Recent genetic studies have identified alleles associated with opposite effects on adiposity and risk of type 2 diabetes. We aimed to identify more of these variants and test the hypothesis that such favorable adiposity alleles are associated with higher subcutaneous fat and lower ectopic fat. We combined MRI data with genome-wide association studies of body fat percentage (%) and metabolic traits. We report 14 alleles, including 7 newly characterized alleles, associated with higher adiposity but a favorable metabolic profile. Consistent with previous studies, individuals carrying more favorable adiposity alleles had higher body fat % and higher BMI but lower risk of type 2 diabetes, heart disease, and hypertension. These individuals also had higher subcutaneous fat but lower liver fat and a lower visceral-to-subcutaneous adipose tissue ratio. Individual alleles associated with higher body fat % but lower liver fat and lower risk of type 2 diabetes included those in PPARGGRB14, and IRS1, whereas the allele in ANKRD55 was paradoxically associated with higher visceral fat but lower risk of type 2 diabetes. Most identified favorable adiposity alleles are associated with higher subcutaneous and lower liver fat, a mechanism consistent with the beneficial effects of storing excess triglycerides in metabolically low-risk depots.

  • 121. Jimenez-Corona, Aida
    et al.
    Nelson, Robert G.
    Jimenez-Corona, Maria E.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Aguilar-Salinas, Carlos A.
    Graue-Hernandez, Enrique O.
    Hernandez-Jimenez, Sergio
    Hernandez-Avila, Mauricio
    Disparities in prediabetes and type 2 diabetes prevalence between indigenous and nonindigenous populations from Southeastern Mexico: The Comitan Study2019Ingår i: JOURNAL OF CLINICAL AND TRANSLATIONAL ENDOCRINOLOGY, ISSN 2214-6237, Vol. 16, artikel-id 100191Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims: In this research we assessed the prevalence of prediabetes and type 2 diabetes and its association with social determinants such as indigenous origin and residence area in population from Comitan, Chiapas, Mexico. Methods: The Comitan Study is a population-based study carried out from 2010 to 2012 that included 1844 participants aged >= 20 years, 880 indigenous and 964 nonindigenous participants. Ethnicity was ascertained by self-report and speaking an indigenous language was also recorded. Prediabetes was defined as fasting serum glucose 5.6-6.9 mmol/l or 2-hour post load serum glucose 7.8-11.0 mmol/l. Type 2 diabetes was defined as fasting serum glucose >= 7.0 mmol/l or 2-h post load serum glucose >= 11.1 mmol/l or previous clinical diagnosis. Results: Age-sex-adjusted prevalence of prediabetes and type 2 diabetes was 18.0% (95%CI 15.3-20.6) and 11.0% (95%CI 8.9-131.1) in nonindigenous and 10.6% (95%CI 8.4-12.7) and 4.7% (95%CI 3.3-6.1) in indigenous individuals, respectively. After stratifying by ethnicity, in both indigenous and nonindigenous participants the probability of prediabetes and type 2 diabetes increased with age and BMI. In both indigenous and nonindigenous participants the probability of type 2 diabetes was lower in those living in rural compared with urban areas. Conclusions: The prevalence of prediabetes and type 2 diabetes was significantly lower in indigenous than in nonindigenous participants. Also, the prevalence of type 2 diabetes was lower in those living in rural areas. Health benefits of a traditional lifestyle may partially account for these differences.

  • 122. Johnson, Steven T
    et al.
    Newton, Amanda S
    Chopra, Meera
    Buckingham, Jeanette
    Huang, Terry T K
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Jetha, Mary M
    Ball, Geoff D C
    In search of quality evidence for lifestyle management and glycemic control in children and adolescents with type 2 diabetes: a systematic review2010Ingår i: BMC Pediatrics, ISSN 1471-2431, E-ISSN 1471-2431, Vol. 10, s. 97-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    There is no high quality evidence to suggest lifestyle modification improves either short- or long-term glycemic control in children and youth with T2D. Additional research is clearly warranted to define optimal lifestyle behaviour strategies for young people with T2D.

  • 123. Jonsson, A
    et al.
    Renström, Frida
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Lyssenko, V
    Brito, Ema C
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Isomaa, B
    Berglund, G
    Nilsson, P M
    Groop, L
    Franks, Paul W
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Assessing the effect of interaction between an FTO variant (rs9939609) and physical activity on obesity in 15,925 Swedish and 2,511 Finnish adults.2009Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 52, nr 7, s. 1334-1338Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIMS/HYPOTHESIS: Recent reports have suggested that genotypes at the FTO locus interact with physical activity to modify levels of obesity-related traits. We tested this hypothesis in two non-diabetic population-based cohorts, the first from southern Sweden and the second from the Botnia region of western Finland. METHODS: In total 2,511 Finnish and 15,925 Swedish non-diabetic middle-aged adults were genotyped for the FTO rs9939609 variant. Physical activity was assessed by questionnaires and standard clinical procedures were conducted, including measures of height and weight and glucose regulation. Tests of gene x physical activity interaction were performed using linear interaction effects to determine whether the effect of this variant on BMI is modified by physical activity. RESULTS: The minor A allele at rs9939609 was associated with higher BMI in both cohorts, with the per allele difference in BMI being about 0.13 and 0.43 kg/m(2) in the Swedish and Finnish cohorts, respectively (p < 0.0001). The test of interaction between physical activity and the rs9939609 variant on BMI was not statistically significant after controlling for age and sex in either cohort (Sweden: p = 0.71, Finland: p = 0.18). CONCLUSIONS/INTERPRETATION: The present report does not support the notion that physical activity modifies the effects of the FTO rs9939609 variant on obesity risk in the non-diabetic Swedish or Finnish adults studied here.

  • 124. Jonsson, Anna
    et al.
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Obesity, FTO gene variant, and energy intake in children.2009Övrigt (Övrigt vetenskapligt)
  • 125. Justice, Anne E.
    et al.
    Karaderi, Tugce
    Highland, Heather M.
    Young, Kristin L.
    Graff, Mariaelisa
    Lu, Yingchang
    Turcot, Valerie
    Auer, Paul L.
    Fine, Rebecca S.
    Guo, Xiuqing
    Schurmann, Claudia
    Lempradl, Adelheid
    Marouli, Eirini
    Mahajan, Anubha
    Winkler, Thomas W.
    Locke, Adam E.
    Medina-Gomez, Carolina
    Esko, Tonu
    Vedantam, Sailaja
    Giri, Ayush
    Lo, Ken Sin
    Alfred, Tamuno
    Mudgal, Poorva
    Ng, Maggie C. Y.
    Heard-Costa, Nancy L.
    Feitosa, Mary F.
    Manning, Alisa K.
    Willems, Sara M.
    Sivapalaratnam, Suthesh
    Abecasis, Goncalo
    Alam, Dewan S.
    Allison, Matthew
    Amouyel, Philippe
    Arzumanyanm, Zorayr
    Balkau, Beverley
    Bastarache, Lisa
    Bergmann, Sven
    Bielak, Lawrence F.
    Blueher, Matthias
    Boehnke, Michael
    Boeing, Heiner
    Boerwinkle, Eric
    Boeger, Carsten A.
    Bork-Jensen, Jette
    Bottinger, Erwin P.
    Bowden, Donald W.
    Brandslund, Ivan
    Broer, Linda
    Burt, Amber A.
    Butterworth, Adam S.
    Caulfield, Markj
    Cesana, Giancarlo
    Chambers, John C.
    Chasman, Daniel, I
    Chen, Yii-Der Ida
    Chowdhury, Rajiv
    Christensen, Cramer
    Chu, Audreyy
    Collins, Francis S.
    Cook, James P.
    Cox, Amanda J.
    Crosslin, David S.
    Danesh, John
    de Bakker, Paul I. W.
    de Denus, Simon
    de Mutsert, Renee
    Dedoussis, George
    Demerath, Ellen W.
    Dennis, Joe G.
    Denny, Josh C.
    Di Angelantonio, Emanuele
    Doerr, Marcus
    Drenos, Fotios
    Dube, Marie-Pierre
    Dunning, Alison M.
    Easton, Douglas F.
    Elliott, Paul
    Evangelou, Evangelos
    Farmaki, Aliki-Eleni
    Feng, Shuang
    Ferrannini, Ele
    Ferrieres, Jean
    Florez, Jose C.
    Fornage, Myriam
    Fox, Caroline S.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmo, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
    Friedrich, Nele
    Gan, Wei
    Gandin, Ilaria
    Gasparini, Paolo
    Giedraitis, Vilmantas
    Girotto, Giorgia
    Gorski, Mathias
    Grallert, Harald
    Grarup, Niels
    Groves, Megan L.
    Gustafsson, Stefan
    Haessler, Jeff
    Hansen, Torben
    Hattersley, Andrew T.
    Hayward, Caroline
    Heid, Iris M.
    Holmen, Oddgeir L.
    Hovingh, G. Kees
    Howson, Joanna M. M.
    Hu, Yao
    Hung, Yi-Jen
    Hveem, Kristian
    Ikram, M. Arfan
    Ingelsson, Erik
    Jackson, Anne U.
    Jarvik, Gail P.
    Jia, Yucheng
    Jorgensen, Torben
    Jousilahti, Pekka
    Justesen, Johanne M.
    Kahali, Bratati
    Karaleftheri, Maria
    Kardia, Sharon L. R.
    Karpe, Fredrik
    Kee, Frank
    Kitajima, Hidetoshi
    Komulainen, Pirjo
    Kooner, Jaspal S.
    Kovacs, Peter
    Kraemer, Bernhard K.
    Kuulasmaa, Kari
    Kuusisto, Johanna
    Laakso, Markku
    Lakka, Timo A.
    Lamparter, David
    La Nge, Leslie A.
    Langenberg, Claudia
    Larson, Eric B.
    Lee, Nanette R.
    Lee, Wen-Jane
    Lehtimaeki, Terho
    Lewis, Cora E.
    Li, Huaixing
    Li, Jin
    RuifangLi-Gao,
    Lin, Li-An
    Lin, Xu
    Lind, Lars
    Lindstroem, Jaana
    Linneberg, Allan
    Liu, Ching-Ti
    Liu, Dajiang J.
    Luan, Jian'an
    Lyytikainen, Leo-Pekka
    MacGregor, Stuart
    Magi, Reedik
    Mannisto, Satu
    Marenne, Gaelle
    Marten, Jonathan
    Mascal, Nicholas G. D.
    McCarthy, Mark, I
    Meidtner, Karina
    Mihailov, Evelin
    Moilanen, Leena
    Moitry, Marie
    Mook-Kanamori, Dennis O.
    Morgan, Anna
    Morris, Andrew P.
    Mueller-Nurasyid, Martina
    Munroe, Patricia B.
    Narisu, Narisu
    Nelson, Christopher P.
    Neville, Matt
    Ntalla, Ioanna
    Owen, Katharine R.
    Pedersen, Oluf
    Peloso, Gina M.
    Pennell, Craig E.
    Perola, Markus
    James, A.
    Perry, John R. B.
    Pers, Tune H.
    Ewing, Ailith
    Polasek, Ozren
    Rasheed, Asif
    Raulerson, Chelsea K.
    Rauramaa, Rainer
    Reilly, Dermot F.
    Reiner, Alex P.
    Ridker, Paul M.
    Rivas, Manuel A.
    Robertson, Neil R.
    Robino, Antonietta
    Rudan, Igor
    Ruth, Katherine S.
    Saleheen, Danish
    Salomaa, Veikko
    Samani, Nilesh J.
    Schreiner, Pamela J.
    Schulze, Matthias B.
    Scott, Robert A.
    Segura-Lepe, Marcelo
    Sim, Xueling
    Slater, Andrew J.
    Small, Kerrin S.
    Smith, Blair H.
    Smith, Jennifer A.
    Southam, Lorraine
    Spector, Timothy D.
    Speliotes, Elizabeth K.
    Stefansson, Kari
    Steinthorsdottir, Valgerdur
    Stirrups, Kathleen E.
    Strauch, Konstantin
    Stringham, Heather M.
    Stumvoll, Michael
    Sun, Liang
    Surendran, Praveen
    Swart, Karin M. A.
    Tardif, Jean-Claude
    Taylor, Kent D.
    Teumer, Alexander
    Thompson, Deborah J.
    Thorleifsson, Gudmar
    Thorsteinsdottir, Unnur
    Thuesen, Betina H.
    Toenjes, Anke
    Torres, Mina
    Tsafantakis, Emmanouil
    Tuomilehto, Jaakko
    Uitterlinden, Andre G.
    Uusitupa, Matti
    van Duijn, Cornelia M.
    Vanhala, Mauno
    Varma, Rohit
    Vermeulen, Sita H.
    Vestergaard, Henrik
    Vitart, Veronique
    Vogt, Thomas F.
    Vuckovic, Dragana
    Wagenknecht, Lynne E.
    Walker, Mark
    Wallentin, Lars
    Wang, Feijie
    Wang, Carol A.
    Wang, Shuai
    Wareham, N. Icholas J.
    Warren, Helen R.
    Waterworth, Dawn M.
    Wessel, Jennifer
    White, Harvey D.
    Willer, Cristen J.
    Wilson, James G.
    Wood, Andrew R.
    Wu, Ying
    Yaghootkar, Hanieh
    Yao, Jie
    Verges-Armstrong, Laura M.
    Young, Robin
    Zeggini, Eleftheria
    Zhan, Xiaowei
    Zhang, Weihua
    Zhao, Jing Hua
    Zhao, Wei
    Zheng, He
    Zhou, Wei
    Zillikens, M. Carola
    Rivadeneira, Fernando
    Borecki, Ingrid B.
    Pospisilik, J. Andrew
    Deloukas, Panos
    Frayling, Timothy M.
    Lettre, Guillaume
    Mohlke, Karen L.
    Rotter, Jerome, I
    Kutalik, Zoltan
    Hirschhorn, Joel N.
    Cupples, L. Adrienne
    Loos, Ruth J. F.
    North, Kari E.
    Lindgren, Cecilia M.
    O'Connell, Jeffrey R.
    Raitakari, Olli T.
    Lange, Leslie A.
    Uitterlinden, Andr G.
    Grove, Megan L.
    Masca, Nicholas G. D.
    Luan, Jianan
    Wareham, Nicholas J.
    Esko, Tnu
    De Bakker, Paul Iw
    Caulfield, Mark J.
    Mller-Nurasyid, Martina
    Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution2019Ingår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 51, nr 3, s. 452-469Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF >= 5%) and nine low-frequency or rare (MAF < 5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.

  • 126. Justice, Anne E
    et al.
    Winkler, Thomas W
    Feitosa, Mary F
    Graff, Misa
    Fisher, Virginia A
    Young, Kristin
    Barata, Llilda
    Deng, Xuan
    Czajkowski, Jacek
    Hadley, David
    Ngwa, Julius S
    Ahluwalia, Tarunveer S
    Chu, Audrey Y
    Heard-Costa, Nancy L
    Lim, Elise
    Perez, Jeremiah
    Eicher, John D
    Kutalik, Zoltan
    Xue, Luting
    Mahajan, Anubha
    Renström, Frida
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, SE-205 02 Malmö, Sweden.
    Wu, Joseph
    Qi, Qibin
    Ahmad, Shafqat
    Alfred, Tamuno
    Amin, Najaf
    Bielak, Lawrence F
    Bonnefond, Amelie
    Bragg, Jennifer
    Cadby, Gemma
    Chittani, Martina
    Coggeshall, Scott
    Corre, Tanguy
    Direk, Nese
    Eriksson, Joel
    Fischer, Krista
    Gorski, Mathias
    Neergaard Harder, Marie
    Horikoshi, Momoko
    Huang, Tao
    Huffman, Jennifer E
    Jackson, Anne U
    Justesen, Johanne Marie
    Kanoni, Stavroula
    Kinnunen, Leena
    Kleber, Marcus E
    Komulainen, Pirjo
    Kumari, Meena
    Lim, Unhee
    Luan, Jian'an
    Lyytikainen, Leo-Pekka
    Mangino, Massimo
    Manichaikul, Ani
    Marten, Jonathan
    Middelberg, Rita P S
    Muller-Nurasyid, Martina
    Navarro, Pau
    Perusse, Louis
    Pervjakova, Natalia
    Sarti, Cinzia
    Smith, Albert Vernon
    Smith, Jennifer A
    Stancakova, Alena
    Strawbridge, Rona J
    Stringham, Heather M
    Sung, Yun Ju
    Tanaka, Toshiko
    Teumer, Alexander
    Trompet, Stella
    van der Laan, Sander W
    van der Most, Peter J
    Van Vliet-Ostaptchouk, Jana V
    Vedantam, Sailaja L
    Verweij, Niek
    Vink, Jacqueline M
    Vitart, Veronique
    Wu, Ying
    Yengo, Loic
    Zhang, Weihua
    Hua Zhao, Jing
    Zimmermann, Martina E
    Zubair, Niha
    Abecasis, Goncalo R
    Adair, Linda S
    Afaq, Saima
    Afzal, Uzma
    Bakker, Stephan J L
    Bartz, Traci M
    Beilby, John
    Bergman, Richard N
    Bergmann, Sven
    Biffar, Reiner
    Blangero, John
    Boerwinkle, Eric
    Bonnycastle, Lori L
    Bottinger, Erwin
    Braga, Daniele
    Buckley, Brendan M
    Buyske, Steve
    Campbell, Harry
    Chambers, John C
    Collins, Francis S
    Curran, Joanne E
    de Borst, Gert J
    de Craen, Anton J M
    de Geus, Eco J C
    Dedoussis, George
    Delgado, Graciela E
    den Ruijter, Hester M
    Eiriksdottir, Gudny
    Eriksson, Anna L
    Esko, Tonu
    Faul, Jessica D
    Ford, Ian
    Forrester, Terrence
    Gertow, Karl
    Gigante, Bruna
    Glorioso, Nicola
    Gong, Jian
    Grallert, Harald
    Grammer, Tanja B
    Grarup, Niels
    Haitjema, Saskia
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Hamsten, Anders
    Hansen, Torben
    Harris, Tamara B
    Hartman, Catharina A
    Hassinen, Maija
    Hastie, Nicholas D
    Heath, Andrew C
    Hernandez, Dena
    Hindorff, Lucia
    Hocking, Lynne J
    Hollensted, Mette
    Holmen, Oddgeir L
    Homuth, Georg
    Jan Hottenga, Jouke
    Huang, Jie
    Hung, Joseph
    Hutri-Kahonen, Nina
    Ingelsson, Erik
    James, Alan L
    Jansson, John-Olov
    Jarvelin, Marjo-Riitta
    Jhun, Min A
    Jorgensen, Marit E
    Juonala, Markus
    Kahonen, Mika
    Karlsson, Magnus
    Koistinen, Heikki A
    Kolcic, Ivana
    Kolovou, Genovefa
    Kooperberg, Charles
    Kramer, Bernhard K
    Kuusisto, Johanna
    Kvaloy, Kirsti
    Lakka, Timo A
    Langenberg, Claudia
    Launer, Lenore J
    Leander, Karin
    Lee, Nanette R
    Lind, Lars
    Lindgren, Cecilia M
    Linneberg, Allan
    Lobbens, Stephane
    Loh, Marie
    Lorentzon, Mattias
    Luben, Robert
    Lubke, Gitta
    Ludolph-Donislawski, Anja
    Lupoli, Sara
    Madden, Pamela A F
    Mannikko, Reija
    Marques-Vidal, Pedro
    Martin, Nicholas G
    McKenzie, Colin A
    McKnight, Barbara
    Mellstrom, Dan
    Menni, Cristina
    Montgomery, Grant W
    Musk, Aw Bill
    Narisu, Narisu
    Nauck, Matthias
    Nolte, Ilja M
    Oldehinkel, Albertine J
    Olden, Matthias
    Ong, Ken K
    Padmanabhan, Sandosh
    Peyser, Patricia A
    Pisinger, Charlotta
    Porteous, David J
    Raitakari, Olli T
    Rankinen, Tuomo
    Rao, D C
    Rasmussen-Torvik, Laura J
    Rawal, Rajesh
    Rice, Treva
    Ridker, Paul M
    Rose, Lynda M
    Bien, Stephanie A
    Rudan, Igor
    Sanna, Serena
    Sarzynski, Mark A
    Sattar, Naveed
    Savonen, Kai
    Schlessinger, David
    Scholtens, Salome
    Schurmann, Claudia
    Scott, Robert A
    Sennblad, Bengt
    Siemelink, Marten A
    Silbernagel, Gunther
    Slagboom, P Eline
    Snieder, Harold
    Staessen, Jan A
    Stott, David J
    Swertz, Morris A
    Swift, Amy J
    Taylor, Kent D
    Tayo, Bamidele O
    Thorand, Barbara
    Thuillier, Dorothee
    Tuomilehto, Jaakko
    Uitterlinden, Andre G
    Vandenput, Liesbeth
    Vohl, Marie-Claude
    Volzke, Henry
    Vonk, Judith M
    Waeber, Gerard
    Waldenberger, Melanie
    Westendorp, R G J
    Wild, Sarah
    Willemsen, Gonneke
    Wolffenbuttel, Bruce H R
    Wong, Andrew
    Wright, Alan F
    Zhao, Wei
    Zillikens, M Carola
    Baldassarre, Damiano
    Balkau, Beverley
    Bandinelli, Stefania
    Boger, Carsten A
    Boomsma, Dorret I
    Bouchard, Claude
    Bruinenberg, Marcel
    Chasman, Daniel I
    Chen, Yii-DerIda
    Chines, Peter S
    Cooper, Richard S
    Cucca, Francesco
    Cusi, Daniele
    Faire, Ulf de
    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, SE-205 02 Malmö, Sweden; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, USA.
    Froguel, Philippe
    Gordon-Larsen, Penny
    Grabe, Hans-Jorgen
    Gudnason, Vilmundur
    Haiman, Christopher A
    Hayward, Caroline
    Hveem, Kristian
    Johnson, Andrew D
    Wouter Jukema, J
    Kardia, Sharon L R
    Kivimaki, Mika
    Kooner, Jaspal S
    Kuh, Diana
    Laakso, Markku
    Lehtimaki, Terho
    Marchand, Loic Le
    Marz, Winfried
    McCarthy, Mark I
    Metspalu, Andres
    Morris, Andrew P
    Ohlsson, Claes
    Palmer, Lyle J
    Pasterkamp, Gerard
    Pedersen, Oluf
    Peters, Annette
    Peters, Ulrike
    Polasek, Ozren
    Psaty, Bruce M
    Qi, Lu
    Rauramaa, Rainer
    Smith, Blair H
    Sorensen, Thorkild I A
    Strauch, Konstantin
    Tiemeier, Henning
    Tremoli, Elena
    van der Harst, Pim
    Vestergaard, Henrik
    Vollenweider, Peter
    Wareham, Nicholas J
    Weir, David R
    Whitfield, John B
    Wilson, James F
    Tyrrell, Jessica
    Frayling, Timothy M
    Barroso, Ines
    Boehnke, Michael
    Deloukas, Panagiotis
    Fox, Caroline S
    Hirschhorn, Joel N
    Hunter, David J
    Spector, Tim D
    Strachan, David P
    van Duijn, Cornelia M
    Heid, Iris M
    Mohlke, Karen L
    Marchini, Jonathan
    Loos, Ruth J F
    Kilpelainen, Tuomas O
    Liu, Ching-Ti
    Borecki, Ingrid B
    North, Kari E
    Cupples, L Adrienne
    Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits2017Ingår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 8, s. 14977-14977Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.

  • 127. Kanoni, Stavroula
    et al.
    Nettleton, Jennifer A
    Hivert, Marie-France
    Ye, Zheng
    van Rooij, Frank JA
    Shungin, Dmitry
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Umeå universitet, Medicinska fakulteten, Institutionen för odontologi. Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Sonestedt, Emily
    Ngwa, Julius S
    Wojczynski, Mary K
    Lemaitre, Rozenn N
    Gustafsson, Stefan
    Anderson, Jennifer S
    Tanaka, Toshiko
    Hindy, George
    Saylor, Georgia
    Renström, Frida
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Clinical Sciences, Lund University, Malmö, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts.
    Bennett, Amanda J
    van Duijn, Cornelia M
    Florez, Jose C
    Fox, Caroline S
    Hofman, Albert
    Hoogeveen, Ron C
    Houston, Denise K
    Hu, Frank B
    Jacques, Paul F
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Lind, Lars
    Liu, Yongmei
    McKeown, Nicola
    Ordovas, Jose
    Pankow, James S
    Sijbrands, Eric JG
    Syvänen, Ann-Christine
    Uitterlinden, André G
    Yannakoulia, Mary
    Zillikens, M Carola
    Wareham, Nick J
    Prokopenko, Inga
    Bandinelli, Stefania
    Forouhi, Nita G
    Cupples, L Adrienne
    Loos, Ruth J
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Dupuis, Josée
    Langenberg, Claudia
    Ferrucci, Luigi
    Kritchevsky, Stephen B
    McCarthy, Mark I
    Ingelsson, Erik
    Borecki, Ingrid B
    Witteman, Jacqueline CM
    Orho-Melander, Marju
    Siscovick, David S
    Meigs, James B
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Clinical Sciences, Lund University, Malmö, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts.
    Dedoussis, George V
    Total zinc intake may modify the glucose-raising effect of a zinc transporter (SLC30A8) variant: a 14-cohort meta-analysis2011Ingår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 60, nr 9, s. 2407-2416Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE Many genetic variants have been associated with glucose homeostasis and type 2 diabetes in genome-wide association studies. Zinc is an essential micronutrient that is important for β-cell function and glucose homeostasis. We tested the hypothesis that zinc intake could influence the glucose-raising effect of specific variants.

    RESEARCH DESIGN AND METHODS We conducted a 14-cohort meta-analysis to assess the interaction of 20 genetic variants known to be related to glycemic traits and zinc metabolism with dietary zinc intake (food sources) and a 5-cohort meta-analysis to assess the interaction with total zinc intake (food sources and supplements) on fasting glucose levels among individuals of European ancestry without diabetes.

    RESULTS We observed a significant association of total zinc intake with lower fasting glucose levels (β-coefficient ± SE per 1 mg/day of zinc intake: -0.0012 ± 0.0003 mmol/L, summary P value = 0.0003), while the association of dietary zinc intake was not significant. We identified a nominally significant interaction between total zinc intake and the SLC30A8 rs11558471 variant on fasting glucose levels (β-coefficient ± SE per A allele for 1 mg/day of greater total zinc intake: -0.0017 ± 0.0006 mmol/L, summary interaction P value = 0.005); this result suggests a stronger inverse association between total zinc intake and fasting glucose in individuals carrying the glucose-raising A allele compared with individuals who do not carry it. None of the other interaction tests were statistically significant.

    CONCLUSIONS Our results suggest that higher total zinc intake may attenuate the glucose-raising effect of the rs11558471 SLC30A8 (zinc transporter) variant. Our findings also support evidence for the association of higher total zinc intake with lower fasting glucose levels.

  • 128. Kato, Norihiro
    et al.
    Loh, Marie
    Takeuchi, Fumihiko
    Verweij, Niek
    Wang, Xu
    Zhang, Weihua
    Kelly, Tanika N.
    Saleheen, Danish
    Lehne, Benjamin
    Leach, Irene Mateo
    Drong, Alexander W.
    Abbott, James
    Wahl, Simone
    Tan, Sian-Tsung
    Scott, William R.
    Campanella, Gianluca
    Chadeau-Hyam, Marc
    Afzal, Uzma
    Ahluwalia, Tarunveer S.
    Bonder, Marc Jan
    Chen, Peng
    Dehghan, Abbas
    Edwards, Todd L.
    Esko, Tonu
    Go, Min Jin
    Harris, Sarah E.
    Hartiala, Jaana
    Kasela, Silva
    Kasturiratne, Anuradhani
    Khor, Chiea-Chuen
    Kleber, Marcus E.
    Li, Huaixing
    Mok, Zuan Yu
    Nakatochi, Masahiro
    Sapari, Nur Sabrina
    Saxena, Richa
    Stewart, Alexandre F. R.
    Stolk, Lisette
    Tabara, Yasuharu
    Teh, Ai Ling
    Wu, Ying
    Wu, Jer-Yuarn
    Zhang, Yi
    Aits, Imke
    Alves, Alexessander Da Silva Couto
    Das, Shikta
    Dorajoo, Rajkumar
    Hopewell, Jemma C.
    Kim, Yun Kyoung
    Koivula, Robert W.
    Luan, Jian'an
    Lyytikainen, Leo-Pekka
    Nguyen, Quang N.
    Pereira, Mark A.
    Postmus, Iris
    Raitakari, Olli T.
    Bryan, Molly Scannell
    Scott, Robert A.
    Sorice, Rossella
    Tragante, Vinicius
    Traglia, Michela
    White, Jon
    Yamamoto, Ken
    Zhang, Yonghong
    Adair, Linda S.
    Ahmed, Alauddin
    Akiyama, Koichi
    Asif, Rasheed
    Aung, Tin
    Barroso, Ines
    Bjonnes, Andrew
    Braun, Timothy R.
    Cai, Hui
    Chang, Li-Ching
    Chen, Chien-Hsiun
    Cheng, Ching-Yu
    Chong, Yap-Seng
    Collins, Rory
    Courtney, Regina
    Davies, Gail
    Delgado, Graciela
    Do, Loi D.
    Doevendans, Pieter A.
    Gansevoort, Ron T.
    Gao, Yu-Tang
    Grammer, Tanja B.
    Grarup, Niels
    Grewal, Jagvir
    Gu, Dongfeng
    Wander, Gurpreet S.
    Hartikainen, Anna-Liisa
    Hazen, Stanley L.
    He, Jing
    Heng, Chew-Kiat
    Hixson, James E.
    Hofman, Albert
    Hsu, Chris
    Huang, Wei
    Husemoen, Lise L. N.
    Hwang, Joo-Yeon
    Ichihara, Sahoko
    Igase, Michiya
    Isono, Masato
    Justesen, Johanne M.
    Katsuy, Tomohiro
    Kibriya, Muhammad G.
    Kim, Young Jin
    Kishimoto, Miyako
    Koh, Woon-Puay
    Kohara, Katsuhiko
    Kumari, Meena
    Kwek, Kenneth
    Lee, Nanette R.
    Lee, Jeannette
    Liao, Jiemin
    Lieb, Wolfgang
    Liewald, David C. M.
    Matsubara, Tatsuaki
    Matsushita, Yumi
    Meitinger, Thomas
    Mihailov, Evelin
    Milani, Lili
    Mills, Rebecca
    Mononen, Nina
    Mueller-Nurasyid, Martina
    Nabika, Toru
    Nakashima, Eitaro
    Ng, Hong Kiat
    Nikus, Kjell
    Nutile, Teresa
    Ohkubo, Takayoshi
    Ohnaka, Keizo
    Parish, Sarah
    Paternoster, Lavinia
    Peng, Hao
    Peters, Annette
    Pham, Son T.
    Pinidiyapathirage, Mohitha J.
    Rahman, Mahfuzar
    Rakugi, Hiromi
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Rozario, Michelle Ann
    Ruggiero, Daniela
    Sala, Cinzia F.
    Sarju, Ralhan
    Shimokawa, Kazuro
    Snieder, Harold
    Sparso, Thomas
    Spiering, Wilko
    Starr, John M.
    Stott, David J.
    Stram, Daniel O.
    Sugiyama, Takao
    Szymczak, Silke
    Tang, W. H. Wilson
    Tong, Lin
    Trompet, Stella
    Turjanmaa, Vaino
    Ueshima, Hirotsugu
    Uitterlinden, Andre G.
    Umemura, Satoshi
    Vaarasmaki, Marja
    van Dam, Rob M.
    van Gilst, Wiek H.
    van Veldhuisen, Dirk J.
    Viikari, Jorma S.
    Waldenberger, Melanie
    Wang, Yiqin
    Wang, Aili
    Wilson, Rory
    Wong, Tien-Yin
    Xiang, Yong-Bing
    Yamaguchi, Shuhei
    Ye, Xingwang
    Young, Robin D.
    Young, Terri L.
    Yuan, Jian-Min
    Zhou, Xueya
    Asselbergs, Folkert W.
    Ciullo, Marina
    Clarke, Robert
    Deloukas, Panos
    Franke, Andre
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin. Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA; Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Skåne University Hospital Malmö, Malmö, Sweden.
    Franks, Steve
    Friedlander, Yechiel
    Gross, Myron D.
    Guo, Zhirong
    Hansen, Torben
    Jarvelin, Marjo-Riitta
    Jorgensen, Torben
    Jukema, J. Wouter
    Kahonen, Mika
    Kajio, Hiroshi
    Kivimaki, Mika
    Lee, Jong-Young
    Lehtimaki, Terho
    Linneberg, Allan
    Miki, Tetsuro
    Pedersen, Oluf
    Samani, Nilesh J.
    Sorensen, Thorkild I. A.
    Takayanagi, Ryoichi
    Toniolo, Daniela
    Ahsan, Habibul
    Allayee, Hooman
    Chen, Yuan-Tsong
    Danesh, John
    Deary, Ian J.
    Franco, Oscar H.
    Franke, Lude
    Heijman, Bastiaan T.
    Holbrook, Joanna D.
    Isaacs, Aaron
    Kim, Bong-Jo
    Lin, Xu
    Liu, Jianjun
    Maerz, Winfried
    Metspalu, Andres
    Mohlke, Karen L.
    Sanghera, Dharambir K.
    Shu, Xiao-Ou
    van Meurs, Joyce B. J.
    Vithana, Eranga
    Wickremasinghe, Ananda R.
    Wijmenga, Cisca
    Wolffenbuttel, Bruce H. W.
    Yokota, Mitsuhiro
    Zheng, Wei
    Zhu, Dingliang
    Vineis, Paolo
    Kyrtopoulos, Soterios A.
    Kleinjans, Jos C. S.
    McCarthy, Mark I.
    Soong, Richie
    Gieger, Christian
    Scott, James
    Teo, Yik-Ying
    He, Jiang
    Elliott, Paul
    Tai, E. Shyong
    van der Harst, Pim
    Kooner, Jaspal S.
    Chambers, John C.
    Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation2015Ingår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 47, nr 11, s. 1282-1293Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.

  • 129. Kilpelainen, Tuomas O.
    et al.
    Bentley, Amy R.
    Noordam, Raymond
    Sung, Yun Ju
    Schwander, Karen
    Winkler, Thomas W.
    Jakupovic, Hermina
    Chasman, Daniel I.
    Manning, Alisa
    Ntalla, Ioanna
    Aschard, Hugues
    Brown, Michael R.
    de las Fuentes, Lisa
    Franceschini, Nora
    Guo, Xiuqing
    Vojinovic, Dina
    Aslibekyan, Stella
    Feitosa, Mary F.
    Kho, Minjung
    Musani, Solomon K.
    Richard, Melissa
    Wang, Heming
    Wang, Zhe
    Bartz, Traci M.
    Bielak, Lawrence F.
    Campbell, Archie
    Dorajoo, Rajkumar
    Fisher, Virginia
    Hartwig, Fernando P.
    Horimoto, Andrea R. V. R.
    Li, Changwei
    Lohman, Kurt K.
    Marten, Jonathan
    Sim, Xueling
    Smith, Albert V.
    Tajuddin, Salman M.
    Alver, Maris
    Amini, Marzyeh
    Boissel, Mathilde
    Chai, Jin Fang
    Chen, Xu
    Divers, Jasmin
    Evangelou, Evangelos
    Gao, Chuan
    Graff, Mariaelisa
    Harris, Sarah E.
    He, Meian
    Hsu, Fang-Chi
    Jackson, Anne U.
    Zhao, Jing Hua
    Kraja, Aldi T.
    Kuehnel, Brigitte
    Laguzzi, Federica
    Lyytikainen, Leo-Pekka
    Nolte, Ilja M.
    Rauramaa, Rainer
    Riaz, Muhammad
    Robino, Antonietta
    Rueedi, Rico
    Stringham, Heather M.
    Takeuchi, Fumihiko
    van der Most, Peter J.
    Varga, Tibor V.
    Verweij, Niek
    Ware, Erin B.
    Wen, Wanqing
    Li, Xiaoyin
    Yanek, Lisa R.
    Amin, Najaf
    Arnett, Donna K.
    Boerwinkle, Eric
    Brumat, Marco
    Cade, Brian
    Canouil, Mickael
    Chen, Yii-Der Ida
    Concas, Maria Pina
    Connell, John
    de Mutsert, Renee
    de Silva, H. Janaka
    de Vries, Paul S.
    Demirkan, Ayse
    Ding, Jingzhong
    Eaton, Charles B.
    Faul, Jessica D.
    Friedlander, Yechiel
    Gabriel, Kelley P.
    Ghanbari, Mohsen
    Giulianini, Franco
    Gu, Chi Charles
    Gu, Dongfeng
    Harris, Tamara B.
    He, Jiang
    Heikkinen, Sami
    Heng, Chew-Kiat
    Hunt, Steven C.
    Ikram, M. Arfan
    Jonas, Jost B.
    Koh, Woon-Puay
    Komulainen, Pirjo
    Krieger, Jose E.
    Kritchevsky, Stephen B.
    Kutalik, Zoltan
    Kuusisto, Johanna
    Langefeld, Carl D.
    Langenberg, Claudia
    Launer, Lenore J.
    Leander, Karin
    Lemaitre, Rozenn N.
    Lewis, Cora E.
    Liang, Jingjing
    Alizadeh, Behrooz Z.
    Boezen, H. Marike
    Franke, Lude
    Navis, Gerjan
    Rots, Marianne
    Swertz, Morris
    Wolffenbuttel, Bruce H. R.
    Wijmenga, Cisca
    Liu, Jianjun
    Magi, Reedik
    Manichaikul, Ani
    Meitinger, Thomas
    Metspalu, Andres
    Milaneschi, Yuri
    Mohlke, Karen L.
    Mosley, Thomas H., Jr.
    Murray, Alison D.
    Nalls, Mike A.
    Nang, Ei-Ei Khaing
    Nelson, Christopher P.
    Nona, Sotoodehnia
    Norris, Jill M.
    Nwuba, Chiamaka Vivian
    O'Connell, Jeff
    Palmer, Nicholette D.
    Papanicolau, George J.
    Pazoki, Raha
    Pedersen, Nancy L.
    Peters, Annette
    Peyser, Patricia A.
    Polasek, Ozren
    Porteous, David J.
    Poveda, Alaitz
    Raitakari, Olli T.
    Rich, Stephen S.
    Risch, Neil
    Robinson, Jennifer G.
    Rose, Lynda M.
    Rudan, Igor
    Schreiner, Pamela J.
    Scott, Robert A.
    Sidney, Stephen S.
    Sims, Mario
    Smith, Jennifer A.
    Snieder, Harold
    Sofer, Tamar
    Starr, John M.
    Sternfeld, Barbara
    Strauch, Konstantin
    Tang, Hua
    Taylor, Kent D.
    Tsai, Michael Y.
    Tuomilehto, Jaakko
    Uitterlinden, Andre G.
    van der Ende, M. Yldau
    van Heemst, Diana
    Voortman, Trudy
    Waldenberger, Melanie
    Wennberg, Patrik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Wilson, Gregory
    Xiang, Yong-Bing
    Yao, Jie
    Yu, Caizheng
    Yuan, Jian-Min
    Zhao, Wei
    Zonderman, Alan B.
    Becker, Diane M.
    Boehnke, Michael
    Bowden, Donald W.
    de Faire, Ulf
    Deary, Ian J.
    Elliott, Paul
    Esko, Tonu
    Freedman, Barry I.
    Froguel, Philippe
    Gasparini, Paolo
    Gieger, Christian
    Kato, Norihiro
    Laakso, Markku
    Lakka, Timo A.
    Lehtimaaki, Terho
    Magnusson, Patrik K. E.
    Oldehinkel, Albertine J.
    Penninx, Brenda W. J. H.
    Samani, Nilesh J.
    Shu, Xiao-Ou
    van der Harst, Pim
    Van Vliet-Ostaptchouk, Jana V.
    Vollenweider, Peter
    Wagenknecht, Lynne E.
    Wang, Ya X.
    Wareham, Nicholas J.
    Weir, David R.
    Wu, Tangchun
    Zheng, Wei
    Zhu, Xiaofeng
    Evans, Michele K.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Skåne University Hospital, Malmö, Sweden; Harvard T. H. Chan School of Public Health, Department of Nutrition, Harvard University, Boston, USA; OCDEM, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
    Gudnason, Vilmundur
    Hayward, Caroline
    Horta, Bernardo L.
    Kelly, Tanika N.
    Liu, Yongmei
    North, Kari E.
    Pereira, Alexandre C.
    Ridker, Paul M.
    Tai, E. Shyong
    van Dam, Rob M.
    Fox, Ervin R.
    Kardia, Sharon L. R.
    Liu, Ching-Ti
    Mook-Kanamori, Dennis O.
    Province, Michael A.
    Redline, Susan
    van Duijn, Cornelia M.
    Rotter, Jerome I.
    Kooperberg, Charles B.
    Gauderman, W. James
    Psaty, Bruce M.
    Rice, Kenneth
    Munroe, Patricia B.
    Fornage, Myriam
    Cupples, L. Adrienne
    Rotimi, Charles N.
    Morrison, Alanna C.
    Rao, Dabeeru C.
    Loos, Ruth J. F.
    Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity2019Ingår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 10, artikel-id 376Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol- increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.

  • 130. Kilpelainen, Tuomas O.
    et al.
    Carli, Jayne F. Martin
    Skowronski, Alicja A.
    Sun, Qi
    Kriebel, Jennifer
    Feitosa, Mary F.
    Hedman, Asa K.
    Drong, Alexander W.
    Hayes, James E.
    Zhao, Jinghua
    Pers, Tune H.
    Schick, Ursula
    Grarup, Niels
    Kutalik, Zoltan
    Trompet, Stella
    Mangino, Massimo
    Kristiansson, Kati
    Beekman, Marian
    Lyytikainen, Leo-Pekka
    Eriksson, Joel
    Henneman, Peter
    Lahti, Jari
    Tanaka, Toshiko
    Luan, Jian'an
    Del Greco M, Fabiola
    Pasko, Dorota
    Renström, Frida
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö 20502, Sweden.
    Willems, Sara M.
    Mahajan, Anubha
    Rose, Lynda M.
    Guo, Xiuqing
    Liu, Yongmei
    Kleber, Marcus E.
    Perusse, Louis
    Gaunt, Tom
    Ahluwalia, Tarunveer S.
    Sung, Yun Ju
    Ramos, Yolande F.
    Amin, Najaf
    Amuzu, Antoinette
    Barroso, Ines
    Bellis, Claire
    Blangero, John
    Buckley, Brendan M.
    Boehringer, Stefan
    Chen, Yii-Der I.
    de Craen, Anton J. N.
    Crosslin, David R.
    Dale, Caroline E.
    Dastani, Zari
    Day, Felix R.
    Deelen, Joris
    Delgado, Graciela E.
    Demirkan, Ayse
    Finucane, Francis M.
    Ford, Ian
    Garcia, Melissa E.
    Gieger, Christian
    Gustafsson, Stefan
    Hallmans, Goran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Hankinson, Susan E.
    Havulinna, Aki S.
    Herder, Christian
    Hernandez, Dena
    Hicks, Andrew A.
    Hunter, David J.
    Illig, Thomas
    Ingelsson, Erik
    Ioan-Facsinay, Andreea
    Jansson, John-Olov
    Jenny, Nancy S.
    Jorgensen, Marit E.
    Jorgensen, Torben
    Karlsson, Magnus
    Koenig, Wolfgang
    Kraft, Peter
    Kwekkeboom, Joanneke
    Laatikainen, Tiina
    Ladwig, Karl-Heinz
    LeDuc, Charles A.
    Lowe, Gordon
    Lu, Yingchang
    Marques-Vidal, Pedro
    Meisinger, Christa
    Menni, Cristina
    Morris, Andrew P.
    Myers, Richard H.
    Mannisto, Satu
    Nalls, Mike A.
    Paternoster, Lavinia
    Peters, Annette
    Pradhan, Aruna D.
    Rankinen, Tuomo
    Rasmussen-Torvik, Laura J.
    Rathmann, Wolfgang
    Rice, Treva K.
    Richards, J. Brent
    Ridker, Paul M.
    Sattar, Naveed
    Savage, David B.
    Söderberg, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Timpson, Nicholas J.
    Vandenput, Liesbeth
    van Heemst, Diana
    Uh, Hae-Won
    Vohl, Marie-Claude
    Walker, Mark
    Wichmann, Heinz-Erich
    Widen, Elisabeth
    Wood, Andrew R.
    Yao, Jie
    Zeller, Tanja
    Zhang, Yiying
    Meulenbelt, Ingrid
    Kloppenburg, Margreet
    Astrup, Arne
    Sorensen, Thorkild I. A.
    Sarzynski, Mark A.
    Rao, D. C.
    Jousilahti, Pekka
    Vartiainen, Erkki
    Hofman, Albert
    Rivadeneira, Fernando
    Uitterlinden, Andre G.
    Kajantie, Eero
    Osmond, Clive
    Palotie, Aarno
    Eriksson, Johan G.
    Heliovaara, Markku
    Knekt, Paul B.
    Koskinen, Seppo
    Jula, Antti
    Perola, Markus
    Huupponen, Risto K.
    Viikari, Jorma S.
    Kahonen, Mika
    Lehtimaki, Terho
    Raitakari, Olli T.
    Mellstrom, Dan
    Lorentzon, Mattias
    Casas, Juan P.
    Bandinelli, Stefanie
    Maerz, Winfried
    Isaacs, Aaron
    van Dijk, Ko W.
    van Duijn, Cornelia M.
    Harris, Tamara B.
    Bouchard, Claude
    Allison, Matthew A.
    Chasman, Daniel I.
    Ohlsson, Claes
    Lind, Lars
    Scott, Robert A.
    Langenberg, Claudia
    Wareham, Nicholas J.
    Ferrucci, Luigi
    Frayling, Timothy M.
    Pramstaller, Peter P.
    Borecki, Ingrid B.
    Waterworth, Dawn M.
    Bergmann, Sven
    Waeber, Gerard
    Vollenweider, Peter
    Vestergaard, Henrik
    Hansen, Torben
    Pedersen, Oluf
    Hu, Frank B.
    Slagboom, P. Eline
    Grallert, Harald
    Spector, Tim D.
    Jukema, J. W.
    Klein, Robert J.
    Schadt, Erik E.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachussetts 02115, USA; Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö 20502, Sweden.
    Lindgren, Cecilia M.
    Leibel, Rudolph L.
    Loos, Ruth J. F.
    Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels2016Ingår i: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 7, artikel-id 10494Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P < 10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P < 5 x 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.

  • 131. Kilpeläinen, Tuomas O
    et al.
    Qi, Lu
    Brage, Soren
    Sharp, Stephen J
    Sonestedt, Emily
    Demerath, Ellen
    Ahmad, Tariq
    Mora, Samia
    Kaakinen, Marika
    Sandholt, Camilla Helene
    Holzapfel, Christina
    Autenrieth, Christine S
    Hyppönen, Elina
    Cauchi, Stéphane
    He, Meian
    Kutalik, Zoltan
    Kumari, Meena
    Stančáková, Alena
    Meidtner, Karina
    Balkau, Beverley
    Tan, Jonathan T
    Mangino, Massimo
    Timpson, Nicholas J
    Song, Yiqing
    Zillikens, M Carola
    Jablonski, Kathleen A
    Garcia, Melissa E
    Johansson, Stefan
    Bragg-Gresham, Jennifer L
    Wu, Ying
    van Vliet-Ostaptchouk, Jana V
    Onland-Moret, N Charlotte
    Zimmermann, Esther
    Rivera, Natalia V
    Tanaka, Toshiko
    Stringham, Heather M
    Silbernagel, Günther
    Kanoni, Stavroula
    Feitosa, Mary F
    Snitker, Soren
    Ruiz, Jonatan R
    Metter, Jeffery
    Larrad, Maria Teresa Martinez
    Atalay, Mustafa
    Hakanen, Maarit
    Amin, Najaf
    Cavalcanti-Proença, Christine
    Grøntved, Anders
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Jansson, John-Olov
    Kuusisto, Johanna
    Kähönen, Mika
    Lutsey, Pamela L
    Nolan, John J
    Palla, Luigi
    Pedersen, Oluf
    Pérusse, Louis
    Renström, Frida
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Scott, Robert A
    Shungin, Dmitry
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Sovio, Ulla
    Tammelin, Tuija H
    Rönnemaa, Tapani
    Lakka, Timo A
    Uusitupa, Matti
    Rios, Manuel Serrano
    Ferrucci, Luigi
    Bouchard, Claude
    Meirhaeghe, Aline
    Fu, Mao
    Walker, Mark
    Borecki, Ingrid B
    Dedoussis, George V
    Fritsche, Andreas
    Ohlsson, Claes
    Boehnke, Michael
    Bandinelli, Stefania
    van Duijn, Cornelia M
    Ebrahim, Shah
    Lawlor, Debbie A
    Gudnason, Vilmundur
    Harris, Tamara B
    Sørensen, Thorkild I A
    Mohlke, Karen L
    Hofman, Albert
    Uitterlinden, André G
    Tuomilehto, Jaakko
    Lehtimäki, Terho
    Raitakari, Olli
    Isomaa, Bo
    Njølstad, Pål R
    Florez, Jose C
    Liu, Simin
    Ness, Andy
    Spector, Timothy D
    Tai, E Shyong
    Froguel, Philippe
    Boeing, Heiner
    Laakso, Markku
    Marmot, Michael
    Bergmann, Sven
    Power, Chris
    Khaw, Kay-Tee
    Chasman, Daniel
    Ridker, Paul
    Hansen, Torben
    Monda, Keri L
    Illig, Thomas
    Järvelin, Marjo-Riitta
    Wareham, Nicholas J
    Hu, Frank B
    Groop, Leif C
    Orho-Melander, Marju
    Ekelund, Ulf
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Loos, Ruth J F
    Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children2011Ingår i: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 8, nr 11, s. e1001116-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n = 218,166) and nine studies of children and adolescents (n = 19,268).

    METHODS AND FINDINGS: All studies identified to have data on the FTO rs9939609 variant (or any proxy [r(2)>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTO×PA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A-) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20-1.26), but PA attenuated this effect (p(interaction)  = 0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio  = 1.22/allele, 95% CI 1.19-1.25) than in the inactive group (odds ratio  = 1.30/allele, 95% CI 1.24-1.36). No such interaction was found in children and adolescents.

    CONCLUSIONS: The association of the FTO risk allele with the odds of obesity is attenuated by 27% in physically active adults, highlighting the importance of PA in particular in those genetically predisposed to obesity.

  • 132. Klüppelholz, Birgit
    et al.
    Thorand, Barbara
    Koenig, Wolfgang
    Gala, Tonia de las Heras
    Meisinger, Christa
    Huth, Cornelia
    Giani, Guido
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Roden, Michael
    Rathmann, Wolfgang
    Peters, Annette
    Herder, Christian
    Association of subclinical inflammation with deterioration of glycaemia before the diagnosis of type 2 diabetes: the KORA S4/F4 study2015Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 58, nr 10, s. 2269-2277Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims/hypothesis The role of biomarkers of subclinical inflammation in the early deterioration of glycaemia before type 2 diabetes is largely unknown. We hypothesised that increased levels of circulating proinflammatory biomarkers and decreased circulating adiponectin would be associated with 7 year increases of HbA1c in non-diabetic individuals.

    Methods This study was based on individuals who participated in the prospective Cooperative Health Research in the Region of Augsburg (KORA) S4 survey (1999–2001) and the 7 year follow-up KORA F4 (2006–2008) survey. Individuals with type 2 diabetes at baseline or with a diagnosis of diabetes in the period between both surveys were excluded, which left a sample of 850 men and women. Multivariable linear regression analyses were performed to assess associations among baseline values of leucocyte count and levels of acute-phase proteins (high-sensitivity C-reactive protein [hsCRP], serum amyloid A [SAA] and fibrinogen), IL-6 and adiponectin with changes in HbA1c between baseline and follow-up.

    Results A high leucocyte count and high hsCRP, SAA and IL-6 levels were positively associated with changes in HbA1c after adjusting for age, sex, lifestyle factors and baseline HbA1c. In contrast, the adiponectin level was inversely associated with changes in HbA1c (p value between <0.0001 and 0.020). The associations of leucocyte count and levels of hsCRP and SAA with HbA1c changes remained significant after additional adjustment for waist circumference and circulating lipids at baseline and for the 7 year change in waist circumference (p value between 0.004 and 0.045).

  • 133. Koivula, R. W.
    et al.
    Grontved, A.
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Wennberg, Patrik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Ostergaard, L.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Renstrom, Frida
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Bicycling to work and primordial prevention of cardiovascular and type 2 diabetes risk: a cohort study from Northern Sweden2016Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 59, s. S150-S150, artikel-id 298Artikel i tidskrift (Refereegranskat)
  • 134. Koivula, Robert W.
    et al.
    Forgie, Ian M.
    Kurbasic, Azra
    Vinuela, Ana
    Heggie, Alison
    Giordano, Giuseppe N.
    Hansen, Tue H.
    Hudson, Michelle
    Koopman, Anitra D. M.
    Rutters, Femke
    Siloaho, Maritta
    Allin, Kristine H.
    Brage, Soren
    Brorsson, Caroline A.
    Dawed, Adem Y.
    De Masi, Federico
    Groves, Christopher J.
    Kokkola, Tarja
    Mahajan, Anubha
    Perry, Mandy H.
    Rauh, Simone P.
    Ridderstrale, Martin
    Teare, Harriet J. A.
    Thomas, E. Louise
    Tura, Andrea
    Vestergaard, Henrik
    White, Tom
    Adamski, Jerzy
    Bell, Jimmy D.
    Beulens, Joline W.
    Brunak, Soren
    Dermitzakis, Emmanouil T.
    Froguel, Philippe
    Frost, Gary
    Gupta, Ramneek
    Hansen, Torben
    Hattersley, Andrew
    Jablonka, Bernd
    Kaye, Jane
    Laakso, Markku
    McDonald, Timothy J.
    Pedersen, Oluf
    Schwenk, Jochen M.
    Pavo, Imre
    Mari, Andrea
    McCarthy, Mark I.
    Ruetten, Hartmut
    Walker, Mark
    Pearson, Ewan
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Department of Clinical Sciences, Lund University Diabetes Centre, Genetic and Molecular Epidemiology Unit, CRC, Skåne University Hospital Malmö, Malmö, Sweden; Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK; Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
    Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes: descriptive characteristics of the epidemiological studies within the IMI DIRECT Consortium2019Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 62, nr 9, s. 1601-1615Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims/hypothesis: Here, we describe the characteristics of the Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) epidemiological cohorts at baseline and follow-up examinations (18, 36 and 48 months of follow-up).

    Methods: From a sampling frame of 24,682 adults of European ancestry enrolled in population-based cohorts across Europe, participants at varying risk of glycaemic deterioration were identified using a risk prediction algorithm (based on age, BMI, waist circumference, use of antihypertensive medication, smoking status and parental history of type 2 diabetes) and enrolled into a prospective cohort study (n = 2127) (cohort 1, prediabetes risk). We also recruited people from clinical registries with type 2 diabetes diagnosed 6-24 months previously (n = 789) into a second cohort study (cohort 2, diabetes). Follow-up examinations took place at similar to 18 months (both cohorts) and at similar to 48 months (cohort 1) or similar to 36 months (cohort 2) after baseline examinations. The cohorts were studied in parallel using matched protocols across seven clinical centres in northern Europe.

    Results: Using ADA 2011 glycaemic categories, 33% (n = 693) of cohort 1 (prediabetes risk) had normal glucose regulation and 67% (n = 1419) had impaired glucose regulation. Seventy-six per cent of participants in cohort 1 was male. Cohort 1 participants had the following characteristics (mean +/- SD) at baseline: age 62 (6.2) years; BMI 27.9 (4.0) kg/m(2); fasting glucose 5.7 (0.6) mmol/l; 2 h glucose 5.9 (1.6) mmol/l. At the final follow-up examination the participants' clinical characteristics were as follows: fasting glucose 6.0 (0.6) mmol/l; 2 h OGTT glucose 6.5 (2.0) mmol/l. In cohort 2 (diabetes), 66% (n = 517) were treated by lifestyle modification and 34% (n = 272) were treated with metformin plus lifestyle modification at enrolment. Fifty-eight per cent of participants in cohort 2 was male. Cohort 2 participants had the following characteristics at baseline: age 62 (8.1) years; BMI 30.5 (5.0) kg/m(2); fasting glucose 7.2 (1.4) mmol/l; 2 h glucose 8.6 (2.8) mmol/l. At the final follow-up examination, the participants' clinical characteristics were as follows: fasting glucose 7.9 (2.0) mmol/l; 2 h mixed-meal tolerance test glucose 9.9 (3.4) mmol/l.

    Conclusions/interpretation: The IMI DIRECT cohorts are intensely characterised, with a wide-variety of metabolically relevant measures assessed prospectively. We anticipate that the cohorts, made available through managed access, will provide a powerful resource for biomarker discovery, multivariate aetiological analyses and reclassification of patients for the prevention and treatment of type 2 diabetes.

  • 135. Koivula, Robert W.
    et al.
    Heggie, Alison
    Barnett, Anna
    Cederberg, Henna
    Hansen, Tue H.
    Koopman, Anitra D.
    Ridderstrale, Martin
    Rutters, Femke
    Vestergaard, Henrik
    Gupta, Ramneek
    Herrgard, Sanna
    Heymans, Martijn W.
    Perry, Mandy H.
    Rauh, Simone
    Siloaho, Maritta
    Teare, Harriet J. A.
    Thorand, Barbara
    Bell, Jimmy
    Brunak, Soren
    Frost, Gary
    Jablonka, Bernd
    Mari, Andrea
    McDonald, Tim J.
    Dekker, Jacqueline M.
    Hansen, Torben
    Hattersley, Andrew
    Laakso, Markku
    Pedersen, Oluf
    Koivisto, Veikko
    Ruetten, Hartmut
    Walker, Mark
    Pearson, Ewan
    Franks, Paul
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes: rationale and design of the epidemiological studies within the IMI DIRECT Consortium2014Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 57, nr 6, s. 1132-1142Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIMS/HYPOTHESIS:

    The DIRECT (Diabetes Research on Patient Stratification) Study is part of a European Union Framework 7 Innovative Medicines Initiative project, a joint undertaking between four industry and 21 academic partners throughout Europe. The Consortium aims to discover and validate biomarkers that: (1) predict the rate of glycaemic deterioration before and after type 2 diabetes onset; (2) predict the response to diabetes therapies; and (3) help stratify type 2 diabetes into clearly definable disease subclasses that can be treated more effectively than without stratification. This paper describes two new prospective cohort studies conducted as part of DIRECT.

    METHODS:

    Prediabetic participants (target sample size 2,200-2,700) and patients with newly diagnosed type 2 diabetes (target sample size ~1,000) are undergoing detailed metabolic phenotyping at baseline and 18 months and 36 months later. Abdominal, pancreatic and liver fat is assessed using MRI. Insulin secretion and action are assessed using frequently sampled OGTTs in non-diabetic participants, and frequently sampled mixed-meal tolerance tests in patients with type 2 diabetes. Biosamples include venous blood, faeces, urine and nail clippings, which, among other biochemical analyses, will be characterised at genetic, transcriptomic, metabolomic, proteomic and metagenomic levels. Lifestyle is assessed using high-resolution triaxial accelerometry, 24 h diet record, and food habit questionnaires.

    CONCLUSIONS/INTERPRETATION:

    DIRECT will yield an unprecedented array of biomaterials and data. This resource, available through managed access to scientists within and outside the Consortium, will facilitate the development of new treatments and therapeutic strategies for the prevention and management of type 2 diabetes

  • 136. Kraja, Aldi T.
    et al.
    Cook, James P.
    Warren, Helen R.
    Surendran, Praveen
    Liu, Chunyu
    Evangelou, Evangelos
    Manning, Alisa K.
    Grarup, Niels
    Drenos, Fotios
    Sim, Xueling
    Smith, Albert Vernon
    Amin, Najaf
    Blakemore, Alexandra I. F.
    Bork-Jensen, Jette
    Brandslund, Ivan
    Farmaki, Aliki-Eleni
    Fava, Cristiano
    Ferreira, Teresa
    Herzig, Karl-Heinz
    Giri, Ayush
    Giulianini, Franco
    Grove, Megan L.
    Guo, Xiuqing
    Harris, Sarah E.
    Have, Christian T.
    Havulinna, Aki S.
    Zhang, He
    Jorgensen, Marit E.
    Karajamaki, AnneMari
    Kooperberg, Charles
    Linneberg, Allan
    Little, Louis
    Liu, Yongmei
    Bonnycastle, Lori L.
    Lu, Yingchang
    Magi, Reedik
    Mahajan, Anubha
    Malerba, Giovanni
    Marioni, Riccardo E.
    Mei, Hao
    Menni, Cristina
    Morrison, Alanna C.
    Padmanabhan, Sandosh
    Palmas, Walter
    Poveda, Alaitz
    Rauramaa, Rainer
    Rayner, Nigel William
    Riaz, Muhammad
    Rice, Ken
    Richard, Melissa A.
    Smith, Jennifer A.
    Southam, Lorraine
    Stancakova, Alena
    Stirrups, Kathleen E.
    Tragante, Vinicius
    Tuomi, Tiinamaija
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Folkhälsan Research Centre, Finland; Department of Endocrinology, Helsinki University Central Hospital, Finland; Finnish Institute for Molecular Medicine (FIMM), Helsinki University, Finland.
    Tzoulald, Ioanna
    Varga, Tibor V.
    Weiss, Stefan
    Yiorkas, Andrianos M.
    Young, Robin
    Zhang, Weihua
    Barnes, Michael R.
    Cabrera, Claudia P.
    Gao, He
    Boehnke, Michael
    Boerwinkle, Eric
    Chambers, John C.
    Connell, John M.
    Christensen, Cramer K.
    de Boer, Rudolf A.
    Deary, Ian J.
    Dedoussis, George
    Deloukas, Panos
    Dominiczak, Anna F.
    Dorr, Marcus
    Joehanes, Roby
    Edwards, Todd L.
    Esko, Tonu
    Fornage, Myriam
    Franceschini, Nora
    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, United States.
    Gambaro, Giovanni
    Groop, Leif
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Hansen, Torben
    Hayward, Caroline
    Heikki, Oksa
    Ingelsson, Erik
    Tuomilehto, Jaakko
    Jarvelin, Marjo-Riitta
    Kardia, Sharon L. R.
    Karpe, Fredrik
    Kooner, Jaspal S.
    Lakka, Timo A.
    Langenberg, Claudia
    Lind, Lars
    Loos, Ruth J. F.
    Laakso, Markku
    McCarthy, Mark I.
    Melander, Olle
    Mohlke, Karen L.
    Moris, Andrwe P.
    Palmer, Colin N. A.
    Pedersen, Oluf
    Polasek, Ozren
    Poulter, Neil R.
    Province, Michael A.
    Psaty, Bruce M.
    Ridker, Paul M.
    Rotter, Jerome I.
    Rudan, Igor
    Salomaa, Veikko
    Samani, Nilesh J.
    Sever, Peter J.
    Skaaby, Tea
    Stafford, Jeanette M.
    Starr, John M.
    van der Harst, Pim
    van der Meer, Peter
    van Duijn, Cornelia M.
    Vergnaud, Anne-Claire
    Gudnason, Vilmundur
    Wareham, Nicholas J.
    Wilson, James G.
    Willer, Cristen J.
    Witte, Daniel R.
    Zeggini, Eleftheria
    Saleheen, Danish
    Butterworth, Adam S.
    Danesh, John
    Asselbergs, Folkert W.
    Wain, Louise V.
    Ehret, Georg B.
    Chasman, Daniel I.
    Caulfield, Mark J.
    Elliott, Paul
    Lindgren, Cecilia M.
    Levy, Daniel
    Newton-Cheh, Christopher
    Munroe, Patricia B.
    Howson, Joanna M. M.
    New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475000 Individuals2017Ingår i: Circulation: Cardiovascular Genetics, ISSN 1942-325X, E-ISSN 1942-3268, Vol. 10, nr 5, artikel-id e001778Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background-Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data. An additional 100 variants yielded suggestive evidence of association. & para;& para;Methods and Results-Here, we augment the sample with 140886 European individuals from the UK Biobank, in whom 77 of the 100 suggestive SNVs were available for association analysis with systolic BP or diastolic BP or pulse pressure. We performed 2 meta-analyses, one in individuals of European, South Asian, African, and Hispanic descent (pan-ancestry, approximate to 475000), and the other in the subset of individuals of European descent (approximate to 423000). Twenty-one SNVs were genome-wide significant (P<5x10(-8) ) for BP, of which 4 are new BP loci: rs9678851 (missense, SLC4A1AP), rs7437940 (AFAP1), rs13303 (missense, STAB1), and rs1055144 (7p15.2). In addition, we identified a potentially independent novel BP-associated SNV, rs3416322 (missense, SYNPO2L) at a known locus, uncorrelated with the previously reported SNVs. Two SNVs are associated with expression levels of nearby genes, and SNVs at 3 loci are associated with other traits. One SNV with a minor allele frequency <0.01, (rs3025380 at DBH) was genome-wide significant.& para;& para;Conclusions-We report 4 novel loci associated with BP regulation, and 1 independent variant at an established BP locus. This analysis highlights several candidate genes with variation that alter protein function or gene expression for potential follow-up.

  • 137. Kroeger, Janine
    et al.
    Meidtner, Karina
    Stefan, Norbert
    Guevara, Marcela
    Kerrison, Nicola D.
    Ardanaz, Eva
    Aune, Dagfinn
    Boeing, Heiner
    Dorronsoro, Miren
    Dow, Courtney
    Fagherazzi, Guy
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Lund University, Malmö, Sweden .
    Freisling, Heinz
    Gunter, Marc J.
    Huerta, José Maria
    Kaaks, Rudolf
    Key, Timothy J.
    Khaw, Kay Tee
    Krogh, Vittorio
    Kuehn, Tilman
    Mancini, Francesca Romana
    Mattiello, Amalia
    Nilsson, Peter M.
    Olsen, Anja
    Overvad, Kim
    Palli, Domenico
    Quiros, J. Ramon
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Sacerdote, Carlotta
    Sala, Nuria
    Salamanca-Fernandez, Elena
    Sluijs, Ivonne
    Spijkerman, Annemieke M. W.
    Tjonneland, Anne
    Tsilidis, Konstantinos K.
    Tumino, Rosario
    van der Schouw, Yvonne T.
    Forouhi, Nita G.
    Sharp, Stephen J.
    Langenberg, Claudia
    Riboli, Elio
    Schulze, Matthias B.
    Wareham, Nicholas J.
    Circulating Fetuin-A and Risk of Type 2 Diabetes: A Mendelian Randomization Analysis2018Ingår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 67, nr 6, s. 1200-1205Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Fetuin-A, a hepatic-origin protein, is strongly positively associated with risk of type 2 diabetes in human observational studies, but it is unknown whether this association is causal. Weaimed to study the potential causal relation of circulating fetuin-A to risk of type 2 diabetes in a Mendelian randomization study with single nucleotide polymorphisms located in the fetuin-A-encoding AHSG gene. We used data from eight European countries of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study including 10,020 incident cases. Plasma fetuin-A concentration was measured in a subset of 965 subcohort participants and 654 case subjects. A genetic score of the AHSG single nucleotide polymorphisms was strongly associated with fetuin-A (28% explained variation). Using the genetic score as instrumental variable of fetuin-A, we observed no significant association of a 50 mu g/mL higher fetuin-A concentration with diabetes risk (hazard ratio 1.02 [95% CI 0.97, 1.07]). Combining our results with those from the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium (12,171 case subjects) also did not suggest a clear significant relation of fetuin-A with diabetes risk. In conclusion, although there is mechanistic evidence for an effect of fetuin-A on insulin sensitivity and secretion, this study does not support a strong, relevant relationship between circulating fetuin-A and diabetes risk in the general population.

  • 138. Kroeger, Janine
    et al.
    Schulze, Matthias B
    Romaguera, Dora
    Guevara, Marcela
    Buijsse, Brian
    Boeing, Heiner
    Beulens, Joline WJ
    Feskens, Edith JM
    Amiano, Pilar
    Ardanaz, Eva
    Agnoli, Claudia
    Buckland, Genevieve
    Clavel-Chapelon, Francoise
    Dahm, Christina C
    Fagherazzi, Guy
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Kaaks, Rudolf
    Key, Timothy J
    Khaw, Kay Tee
    Lajous, Martin
    Mattiello, Amalia
    Menendez Garcia, Virginia
    Navarro, Carmen
    Nilsson, Peter M
    Overvad, Kim
    Palli, Domenico
    Ricceri, Fulvio
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Sanchez, Maria-Jose
    Slimani, Nadia
    Spijkerman, Annemieke MW
    Tjonneland, Anne
    Tumino, Rosario
    van der A, Daphne L
    Langenberg, Claudia
    Sharp, Stephen J
    Forouhi, Nita G
    Riboli, Elio
    Wareham, Nicholas J
    Adherence to predefined dietary patterns and incident type 2 diabetes in European populations: EPIC-InterAct Study2014Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 57, nr 2, s. 321-333Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Few studies have investigated the relationship between predefined dietary patterns and type 2 diabetes incidence; little is known about the generalisability of these associations. We aimed to assess the association between predefined dietary patterns and type 2 diabetes risk in European populations. From among a case-cohort of 12,403 incident diabetes cases and 16,154 subcohort members nested within the prospective European Prospective Investigation into Cancer and Nutrition study, we used data on 9,682 cases and 12,595 subcohort participants from seven countries. Habitual dietary intake was assessed at baseline with country-specific dietary questionnaires. Two diet-quality scores (alternative Healthy Eating Index [aHEI], Dietary Approaches to Stop Hypertension [DASH] score) and three reduced rank regression (RRR)-derived dietary-pattern scores were constructed. Country-specific HRs were calculated and combined using a random-effects meta-analysis. After multivariable adjustment, including body size, the aHEI and DASH scores were not significantly associated with diabetes, although for the aHEI there was a tendency towards an inverse association in countries with higher mean age. We observed inverse associations of the three RRR-derived dietary-pattern scores with diabetes: HRs (95% CIs) for a 1-SD difference were 0.91 (0.86, 0.96), 0.92 (0.84, 1.01) and 0.87 (0.82, 0.92). Random-effects meta-analyses revealed heterogeneity between countries that was explainable by differences in the age of participants or the distribution of dietary intake. Adherence to specific RRR-derived dietary patterns, commonly characterised by high intake of fruits or vegetables and low intake of processed meat, sugar-sweetened beverages and refined grains, may lower type 2 diabetes risk.

  • 139. Kurbasic, Azra
    et al.
    Fraser, Abigail
    Mogren, Ingrid
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi.
    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, Näringsforskning. Department of Clinical Sciences Malmö, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Clinical Sciences Malmö, Lund University, Malmö, Sweden. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA..
    Rich-Edwards, Janet W.
    Timpka, Simon
    Maternal Hypertensive Disorders of Pregnancy and Offspring Risk of Hypertension: A Population-Based Cohort and Sibling Study2019Ingår i: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 32, nr 4, s. 331-334Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Women with a history of hypertensive disorders of pregnancy (HDP) are at increased risk of hypertension, cardiovascular disease, and type 2 diabetes. Offspring from pregnancies complicated by HDP also have worse cardiometabolic status in childhood and young adulthood, but the offspring risk of clinical hypertension in adulthood is largely unknown.

    METHODS: We studied 13,893 first-born adult offspring (49.4% female) who attended a structured population-based primary care visit (The Västerbotten Health Survey) at age 40 years in Sweden between 1994 and 2013. Data on maternal HDP were collected from a population-based birth register. We investigated the association between maternal HDP and the risk of adult offspring hypertension and worse cardiometabolic risk factor status utilizing multivariable poisson and linear regression models. We also conducted a sibling comparison, which inherently accounted for familial factors shared by siblings (N = 135).

    RESULTS: Offspring participants of women with HDP (N = 383, 2.8%) had increased relative risk of hypertension (1.67, 95% confidence interval: 1.38, 2.01) and also higher mean body mass index, systolic blood pressure, diastolic blood pressure, and worse 2-hour 75 g oral glucose tolerance test result at age 40 years. No difference was observed for serum cholesterol. Point estimates for the cardiometabolic risk factors were attenuated in the sibling analyses.

    CONCLUSION: Offspring born to mothers with a history of HDP are on an adverse cardiometabolic trajectory and should be considered as concomitant targets for primordial prevention of hypertension in the maternal post-pregnancy period.

  • 140. Kurbasic, Azra
    et al.
    Poveda, Alaitz
    Chen, Yan
    Ågren, Åsa
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Engberg, Elisabeth
    Umeå universitet, Samhällsvetenskapliga fakulteten, Demografiska databasen.
    Hu, Frank B
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Barroso, Ines
    Brändström, Anders
    Umeå universitet, Samhällsvetenskapliga fakulteten, Demografiska databasen.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Renström, Frida
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
    Gene-Lifestyle Interactions in Complex Diseases: Design and Description of the GLACIER and VIKING Studies2014Ingår i: Current nutrition reports, ISSN 2161-3311, Vol. 3, nr 4, s. 400-411Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Most complex diseases have well-established genetic and non-genetic risk factors. In some instances, these risk factors are likely to interact, whereby their joint effects convey a level of risk that is either significantly more or less than the sum of these risks. Characterizing these gene-environment interactions may help elucidate the biology of complex diseases, as well as to guide strategies for their targeted prevention. In most cases, the detection of gene-environment interactions will require sample sizes in excess of those needed to detect the marginal effects of the genetic and environmental risk factors. Although many consortia have been formed, comprising multiple diverse cohorts to detect gene-environment interactions, few robust examples of such interactions have been discovered. This may be because combining data across studies, usually through meta-analysis of summary data from the contributing cohorts, is often a statistically inefficient approach for the detection of gene-environment interactions. Ideally, single, very large and well-genotyped prospective cohorts, with validated measures of environmental risk factor and disease outcomes should be used to study interactions. The presence of strong founder effects within those cohorts might further strengthen the capacity to detect novel genetic effects and gene-environment interactions. Access to accurate genealogical data would also aid in studying the diploid nature of the human genome, such as genomic imprinting (parent-of-origin effects). Here we describe two studies from northern Sweden (the GLACIER and VIKING studies) that fulfill these characteristics.

  • 141. Körner, A
    et al.
    Ma, L
    Franks, Paul
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Kiess, W
    Baier, L J
    Stumvoll, M
    Kovacs, P
    Sex-specific effect of the Val1483Ile polymorphism in the fatty acid synthase gene (FAS) on body mass index and lipid profile in Caucasian children.2007Ingår i: Int J Obes (Lond), ISSN 0307-0565, Vol. 31, nr 2, s. 353-8Artikel i tidskrift (Refereegranskat)
  • 142. Langenberg, C.
    et al.
    Sharp, S.
    Forouhi, N. G.
    Franks, Paul
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Schulze, M. B.
    Kerrison, N.
    Ekelund, U.
    Barroso, I.
    Panico, S.
    Tormo, M. J.
    Spranger, J.
    Griffin, S.
    van der Schouw, Y. T.
    Amiano, P.
    Ardanaz, E.
    Arriola, L.
    Balkau, B.
    Barricarte, A.
    Beulens, J. W. J.
    Boeing, H.
    Bueno-de-Mesquita, H. B.
    Buijsse, B.
    Chirlaque Lopez, M. D.
    Clavel-Chapelon, F.
    Crowe, F. L.
    de Lauzon-Guillan, B.
    Deloukas, P.
    Dorronsoro, M.
    Drogan, D.
    Froguel, P.
    Gonzalez, C.
    Grioni, S.
    Groop, L.
    Groves, C.
    Hainaut, P.
    Halkjaer, J.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Hansen, T.
    Huerta Castano, J. M.
    Kaaks, R.
    Key, T. J.
    Khaw, K. T.
    Koulman, A.
    Mattiello, A.
    Navarro, C.
    Nilsson, P.
    Norat, T.
    Overvad, K.
    Palla, L.
    Palli, D.
    Pedersen, O.
    Peeters, P. H.
    Quiros, J. R.
    Ramachandran, A.
    Rodriguez-Suarez, L.
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Romaguera, D.
    Romieu, I.
    Sacerdote, C.
    Sanchez, M. J.
    Sandbaek, A.
    Slimani, N.
    Sluijs, I.
    Spijkerman, A. M. W.
    Teucher, B.
    Tjonneland, A.
    Tumino, R.
    van der A, D. L.
    Verschuren, W. M. M.
    Tuomilehto, J.
    Feskens, E.
    McCarthy, M.
    Riboli, E.
    Wareham, N. J.
    Design and cohort description of the InterAct Project: an examination of the interaction of genetic and lifestyle factors on the incidence of type 2 diabetes in the EPIC Study2011Ingår i: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 54, nr 9, s. 2272-2282Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Studying gene-lifestyle interaction may help to identify lifestyle factors that modify genetic susceptibility and uncover genetic loci exerting important subgroup effects. Adequately powered studies with prospective, unbiased, standardised assessment of key behavioural factors for gene-lifestyle studies are lacking. This case-cohort study aims to investigate how genetic and potentially modifiable lifestyle and behavioural factors, particularly diet and physical activity, interact in their influence on the risk of developing type 2 diabetes. Incident cases of type 2 diabetes occurring in European Prospective Investigation into Cancer and Nutrition (EPIC) cohorts between 1991 and 2007 from eight of the ten EPIC countries were ascertained and verified. Prentice-weighted Cox regression and random-effects meta-analyses were used to investigate differences in diabetes incidence by age and sex. A total of 12,403 verified incident cases of type 2 diabetes occurred during 3.99 million person-years of follow-up of 340,234 EPIC participants eligible for InterAct. We defined a centre-stratified subcohort of 16,154 individuals for comparative analyses. Individuals with incident diabetes who were randomly selected into the subcohort (n = 778) were included as cases in the analyses. All prevalent diabetes cases were excluded from the study. InterAct cases were followed-up for an average of 6.9 years; 49.7% were men. Mean baseline age and age at diagnosis were 55.6 and 62.5 years, mean BMI and waist circumference values were 29.4 kg/m(2) and 102.7 cm in men, and 30.1 kg/m(2) and 92.8 cm in women, respectively. Risk of type 2 diabetes increased linearly with age, with an overall HR of 1.56 (95% CI 1.48-1.64) for a 10 year age difference, adjusted for sex. A male excess in the risk of incident diabetes was consistently observed across all countries, with a pooled HR of 1.51 (95% CI 1.39-1.64), adjusted for age. InterAct is a large, well-powered, prospective study that will inform our understanding of the interplay between genes and lifestyle factors on the risk of type 2 diabetes development.

  • 143. Langenberg, Claudia
    et al.
    Sharp, Stephen J.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Lund University, Malmö, Sweden.
    Scott, Robert A.
    Deloukas, Panos
    Forouhi, Nita G.
    Froguel, Philippe
    Groop, Leif C.
    Hansen, Torben
    Palla, Luigi
    Pedersen, Oluf
    Schulze, Matthias B.
    Tormo, Maria-Jose
    Wheeler, Eleanor
    Agnoli, Claudia
    Arriola, Larraitz
    Barricarte, Aurelio
    Boeing, Heiner
    Clarke, Geraldine M.
    Clavel-Chapelon, Francoise
    Duell, Eric J.
    Fagherazzi, Guy
    Kaaks, Rudolf
    Kerrison, Nicola D.
    Key, Timothy J.
    Khaw, Kay Tee
    Kroeger, Janine
    Lajous, Martin
    Morris, Andrew P.
    Navarro, Carmen
    Nilsson, Peter M.
    Overvad, Kim
    Palli, Domenico
    Panico, Salvatore
    Quiros, J. Ramon
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Sacerdote, Carlotta
    Sanchez, Maria-Jose
    Slimani, Nadia
    Spijkerman, Annemieke M. W.
    Tumino, Rosario
    van der A, Daphne L.
    van der Schouw, Yvonne T.
    Barroso, Ines
    McCarthy, Mark I.
    Riboli, Elio
    Wareham, Nicholas J.
    Gene-Lifestyle Interaction and Type 2 Diabetes: the EPIC InterAct Case-Cohort Study2014Ingår i: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 11, nr 5, artikel-id e1001647Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Understanding of the genetic basis of type 2 diabetes (T2D) has progressed rapidly, but the interactions between common genetic variants and lifestyle risk factors have not been systematically investigated in studies with adequate statistical power. Therefore, we aimed to quantify the combined effects of genetic and lifestyle factors on risk of T2D in order to inform strategies for prevention. Methods and Findings: The InterAct study includes 12,403 incident T2D cases and a representative sub-cohort of 16,154 individuals from a cohort of 340,234 European participants with 3.99 million person-years of follow-up. We studied the combined effects of an additive genetic T2D risk score and modifiable and non-modifiable risk factors using Prentice-weighted Cox regression and random effects meta-analysis methods. The effect of the genetic score was significantly greater in younger individuals (p for interaction = 1.20x10(-4)). Relative genetic risk (per standard deviation [4.4 risk alleles]) was also larger in participants who were leaner, both in terms of body mass index (p for interaction = 1.50x10(-3)) and waist circumference (p for interaction = 7.49x10(-9)). Examination of absolute risks by strata showed the importance of obesity for T2D risk. The 10-y cumulative incidence of T2D rose from 0.25% to 0.89% across extreme quartiles of the genetic score in normal weight individuals, compared to 4.22% to 7.99% in obese individuals. We detected no significant interactions between the genetic score and sex, diabetes family history, physical activity, or dietary habits assessed by a Mediterranean diet score. Conclusions: The relative effect of a T2D genetic risk score is greater in younger and leaner participants. However, this subgroup is at low absolute risk and would not be a logical target for preventive interventions. The high absolute risk associated with obesity at any level of genetic risk highlights the importance of universal rather than targeted approaches to lifestyle intervention.

  • 144. Langenberg, Claudia
    et al.
    Sharp, Stephen J.
    Schulze, Matthias B
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Overvad, Kim
    Forouhi, Nita G
    Spranger, Joachim
    Drogan, Dagmar
    Maria Huerta, Jose
    Arriola, Larraitz
    de Lauzon-Guillan, Blandine
    Tormo, Maria-Jose
    Ardanaz, Eva
    Balkau, Beverley
    Beulens, Joline WJ
    Boeing, Heiner
    Bueno-de-Mesquita, H Bas
    Clavel-Chapelon, Francoise
    Crowe, Francesca L
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Gonzalez, Carlos A
    Grioni, Sara
    Halkjaer, Jytte
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Kaaks, Rudolf
    Kerrison, Nicola D
    Key, Timothy J
    Khaw, Kay Tee
    Mattiello, Amalia
    Nilsson, Peter
    Norat, Teresa
    Palla, Luigi
    Palli, Domenico
    Panico, Salvatore
    Ramon Quiros, J
    Romaguera, Dora
    Romieu, Isabelle
    Sacerdote, Carlotta
    Sanchez, Maria-Jose
    Slimani, Nadia
    Sluijs, Ivonne
    Spijkerman, Annemieke MW
    Teucher, Birgit
    Tjonneland, Anne
    Tumino, Rosario
    Daphne, L van der A
    van der Schouw, Yvonne T
    Feskens, Edith JM
    Riboli, Elio
    Wareham, Nicholas J
    Long-term risk of incident type 2 diabetes and measures of overall and regional obesity: the EPIC-interact case-cohort study2012Ingår i: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 9, nr 6, s. e1001230-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Waist circumference (WC) is a simple and reliable measure of fat distribution that may add to the prediction of type 2 diabetes (T2D), but previous studies have been too small to reliably quantify the relative and absolute risk of future diabetes by WC at different levels of body mass index (BMI).

    Methods and Findings: The prospective InterAct case-cohort study was conducted in 26 centres in eight European countries and consists of 12,403 incident T2D cases and a stratified subcohort of 16,154 individuals from a total cohort of 340,234 participants with 3.99 million person-years of follow-up. We used Prentice-weighted Cox regression and random effects meta-analysis methods to estimate hazard ratios for T2D. Kaplan-Meier estimates of the cumulative incidence of T2D were calculated. BMI and WC were each independently associated with T2D, with WC being a stronger risk factor in women than in men. Risk increased across groups defined by BMI and WC; compared to low normal weight individuals (BMI 18.5-22.4 kg/m(2)) with a low WC (< 94/80 cm in men/women), the hazard ratio of T2D was 22.0 (95% confidence interval 14.3; 33.8) in men and 31.8 (25.2; 40.2) in women with grade 2 obesity (BMI >= 35 kg/m(2)) and a high WC (> 102/88 cm). Among the large group of overweight individuals, WC measurement was highly informative and facilitated the identification of a subgroup of overweight people with high WC whose 10-y T2D cumulative incidence (men, 70 per 1,000 person-years; women, 44 per 1,000 person-years) was comparable to that of the obese group (50-103 per 1,000 person-years in men and 28-74 per 1,000 person-years in women).

    Conclusions: WC is independently and strongly associated with T2D, particularly in women, and should be more widely measured for risk stratification. If targeted measurement is necessary for reasons of resource scarcity, measuring WC in overweight individuals may be an effective strategy, since it identifies a high-risk subgroup of individuals who could benefit from individualised preventive action.

  • 145. Li, Sherly X.
    et al.
    Imamura, Fumiaki
    Ye, Zheng
    Schulze, Matthias B.
    Zheng, Jusheng
    Ardanaz, Eva
    Arriola, Larraitz
    Boeing, Heiner
    Dow, Courtney
    Fagherazzi, Guy
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Lund Univ, Sweden.
    Agudo, Antonio
    Grioni, Sara
    Kaaks, Rudolf
    Katzke, Verena A.
    Key, Timothy J.
    Khaw, Kay Tee
    Mancini, Francesca R.
    Navarro, Carmen
    Nilsson, Peter M.
    Onland-Moret, N. Charlotte
    Overvad, Kim
    Palli, Domenico
    Panico, Salvatore
    Quiros, J. Ramon
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Sacerdote, Carlotta
    Sanchez, Maria-Jose
    Slimani, Nadia
    Sluijs, Ivonne
    Spijkerman, Annemieke M. W.
    Tjonneland, Anne
    Tumino, Rosario
    Sharp, Stephen J.
    Riboli, Elio
    Langenberg, Claudia
    Scott, Robert A.
    Forouhi, Nita G.
    Wareham, Nicholas J.
    Interaction between genes and macronutrient intake on the risk of developing type 2 diabetes: systematic review and findings from European Prospective Investigation into Cancer (EPIC)-InterAct2017Ingår i: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 106, nr 1, s. 263-275Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Background: Gene-diet interactions have been reported to contribute to the development of type 2 diabetes (T2D). However, to our knowledge, few examples have been consistently replicated to date. Objective: We aimed to identify existing evidence for genemacronutrient interactions and T2D and to examine the reported interactions in a large-scale study. Design: We systematically reviewed studies reporting genemacronutrient interactions and T2D. We searched the MEDLINE, Human Genome Epidemiology Network, and WHO International Clinical Trials Registry Platform electronic databases to identify studies published up to October 2015. Eligibility criteria included assessment of macronutrient quantity (e.g., total carbohydrate) or indicators of quality (e. g., dietary fiber) by use of self-report or objective biomarkers of intake. Interactions identified in the review were subsequently examined in the EPIC (European Prospective Investigation into Cancer)-InterAct case-cohort study (n = 21,148, with 9403 T2D cases; 8 European countries). Prentice-weighted Cox regression was used to estimate countryspecific HRs, 95% CIs, and P-interaction values, which were then pooled by random-effects meta-analysis. A primary model was fitted by using the same covariates as reported in the published studies, and a second model adjusted for additional covariates and estimated the effects of isocaloric macronutrient substitution. Results: Thirteen observational studies met the eligibility criteria (n < 1700 cases). Eight unique interactions were reported to be significant between macronutrients [carbohydrate, fat, saturated fat, dietary fiber, and glycemic load derived from self-report of dietary intake and circulating n-3 (v-3) polyunsaturated fatty acids] and genetic variants in or near transcription factor 7-like 2 (TCF7L2), gastric inhibitory polypeptide receptor (GIPR), caveolin 2 (CAV2), and peptidase D (PEPD) (P-interaction, 0.05). We found no evidence of interaction when we tried to replicate previously reported interactions. In addition, no interactions were detected in models with additional covariates. Conclusions: Eight gene-macronutrient interactions were identified for the risk of T2D from the literature. These interactions were not replicated in the EPIC-InterAct study, which mirrored the analyses undertaken in the original reports. Our findings highlight the importance of independent replication of reported interactions.

  • 146. Lindgren, Cecilia M
    et al.
    Heid, Iris M
    Randall, Joshua C
    Lamina, Claudia
    Steinthorsdottir, Valgerdur
    Qi, Lu
    Speliotes, Elizabeth K
    Thorleifsson, Gudmar
    Willer, Cristen J
    Herrera, Blanca M
    Jackson, Anne U
    Lim, Noha
    Scheet, Paul
    Soranzo, Nicole
    Amin, Najaf
    Aulchenko, Yurii S
    Chambers, John C
    Drong, Alexander
    Luan, Jian'an
    Lyon, Helen N
    Rivadeneira, Fernando
    Sanna, Serena
    Timpson, Nicholas J
    Zillikens, M Carola
    Zhao, Jing Hua
    Almgren, Peter
    Bandinelli, Stefania
    Bennett, Amanda J
    Bergman, Richard N
    Bonnycastle, Lori L
    Bumpstead, Suzannah J
    Chanock, Stephen J
    Cherkas, Lynn
    Chines, Peter
    Coin, Lachlan
    Cooper, Cyrus
    Crawford, Gabriel
    Doering, Angela
    Dominiczak, Anna
    Doney, Alex S F
    Ebrahim, Shah
    Elliott, Paul
    Erdos, Michael R
    Estrada, Karol
    Ferrucci, Luigi
    Fischer, Guido
    Forouhi, Nita G
    Gieger, Christian
    Grallert, Harald
    Groves, Christopher J
    Grundy, Scott
    Guiducci, Candace
    Hadley, David
    Hamsten, Anders
    Havulinna, Aki S
    Hofman, Albert
    Holle, Rolf
    Holloway, John W
    Illig, Thomas
    Isomaa, Bo
    Jacobs, Leonie C
    Jameson, Karen
    Jousilahti, Pekka
    Karpe, Fredrik
    Kuusisto, Johanna
    Laitinen, Jaana
    Lathrop, G Mark
    Lawlor, Debbie A
    Mangino, Massimo
    McArdle, Wendy L
    Meitinger, Thomas
    Morken, Mario A
    Morris, Andrew P
    Munroe, Patricia
    Narisu, Narisu
    Nordström, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Nordström, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Oostra, Ben A
    Palmer, Colin N A
    Payne, Felicity
    Peden, John F
    Prokopenko, Inga
    Renström, Frida
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Ruokonen, Aimo
    Salomaa, Veikko
    Sandhu, Manjinder S
    Scott, Laura J
    Scuteri, Angelo
    Silander, Kaisa
    Song, Kijoung
    Yuan, Xin
    Stringham, Heather M
    Swift, Amy J
    Tuomi, Tiinamaija
    Uda, Manuela
    Vollenweider, Peter
    Waeber, Gerard
    Wallace, Chris
    Walters, G Bragi
    Weedon, Michael N
    Witteman, Jacqueline C M
    Zhang, Cuilin
    Zhang, Weihua
    Caulfield, Mark J
    Collins, Francis S
    Davey Smith, George
    Day, Ian N M
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Hattersley, Andrew T
    Hu, Frank B
    Jarvelin, Marjo-Riitta
    Kong, Augustine
    Kooner, Jaspal S
    Laakso, Markku
    Lakatta, Edward
    Mooser, Vincent
    Morris, Andrew D
    Peltonen, Leena
    Samani, Nilesh J
    Spector, Timothy D
    Strachan, David P
    Tanaka, Toshiko
    Tuomilehto, Jaakko
    Uitterlinden, André G
    van Duijn, Cornelia M
    Wareham, Nicholas J
    Hugh Watkins,
    Waterworth, Dawn M
    Boehnke, Michael
    Deloukas, Panos
    Groop, Leif
    Hunter, David J
    Thorsteinsdottir, Unnur
    Schlessinger, David
    Wichmann, H-Erich
    Frayling, Timothy M
    Abecasis, Gonçalo R
    Hirschhorn, Joel N
    Loos, Ruth J F
    Stefansson, Kari
    Mohlke, Karen L
    Barroso, Inês
    McCarthy, Mark I
    Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.2009Ingår i: PLoS genetics, ISSN 1553-7404, Vol. 5, nr 6, s. e1000508-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.

  • 147. Liu, Dajiang J.
    et al.
    Peloso, Gina M.
    Yu, Haojie
    Butterworth, Adam S.
    Wang, Xiao
    Mahajan, Anubha
    Saleheen, Danish
    Emdin, Connor
    Alam, Dewan
    Alves, Alexessander Couto
    Amouyel, Philippe
    Di Angelantonio, Emanuele
    Arveiler, Dominique
    Assimes, Themistocles L.
    Auer, Paul L.
    Baber, Usman
    Ballantyne, Christie M.
    Bang, Lia E.
    Benn, Marianne
    Bis, Joshua C.
    Boehnke, Michael
    Boerwinkle, Eric
    Bork-Jensen, Jette
    Bottinger, Erwin P.
    Brandslund, Ivan
    Brown, Morris
    Busonero, Fabio
    Caulfield, Mark J.
    Chambers, John C.
    Chasman, Daniel I.
    Chen, Y. Eugene
    Chen, Yii-Der Ida
    Chowdhury, Rajiv
    Christensen, Cramer
    Chu, Audrey Y.
    Connell, John M.
    Cucca, Francesco
    Cupples, L. Adrienne
    Damrauer, Scott M.
    Davies, Gail
    Deary, Ian J.
    Dedoussis, George
    Denny, Joshua C.
    Dominiczak, Anna
    Dube, Marie-Pierre
    Ebeling, Tapani
    Eiriksdottir, Gudny
    Esko, Tonu
    Farmaki, Aliki-Eleni
    Feitosa, Mary F.
    Ferrario, Marco
    Ferrieres, Jean
    Ford, Ian
    Fornage, Myriam
    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, Massachusetts, USA.
    Frayling, Timothy M.
    Frikke-Schmidt, Ruth
    Fritsche, Lars G.
    Frossard, Philippe
    Fuster, Valentin
    Ganesh, Santhi K.
    Gao, Wei
    Garcia, Melissa E.
    Gieger, Christian
    Giulianini, Franco
    Goodarzi, Mark O.
    Grallert, Harald
    Grarup, Niels
    Groop, Leif
    Grove, Megan L.
    Gudnason, Vilmundur
    Hansen, Torben
    Harris, Tamara B.
    Hayward, Caroline
    Hirschhorn, Joel N.
    Holmen, Oddgeir L.
    Huffman, Jennifer
    Huo, Yong
    Hveem, Kristian
    Jabeen, Sehrish
    Jackson, Anne U.
    Jakobsdottir, Johanna
    Jarvelin, Marjo-Riitta
    Jensen, Gorm B.
    Jorgensen, Marit E.
    Jukema, J. Wouter
    Justesen, Johanne M.
    Kamstrup, Pia R.
    Kanoni, Stavroula
    Karpe, Fredrik
    Kee, Frank
    Khera, Amit V.
    Klarin, Derek
    Koistinen, Heikki A.
    Kooner, Jaspal S.
    Kooperberg, Charles
    Kuulasmaa, Kari
    Kuusisto, Johanna
    Laakso, Markku
    Lakka, Timo
    Langenberg, Claudia
    Langsted, Anne
    Launer, Lenore J.
    Lauritzen, Torsten
    Liewald, David C. M.
    Lin, Li An
    Linneberg, Allan
    Loos, Ruth J. F.
    Lu, Yingchang
    Lu, Xiangfeng
    Magi, Reedik
    Malarstig, Anders
    Manichaikul, Ani
    Manning, Alisa K.
    Mantyselka, Pekka
    Marouli, Eirini
    Masca, Nicholas G. D.
    Maschio, Andrea
    Meigs, James B.
    Melander, Olle
    Metspalu, Andres
    Morris, Andrew P.
    Morrison, Alanna C.
    Mulas, Antonella
    Mueller-Nurasyid, Martina
    Munroe, Patricia B.
    Neville, Matt J.
    Nielsen, Jonas B.
    Nielsen, Sune F.
    Nordestgaard, Borge G.
    Ordovas, Jose M.
    Mehran, Roxana
    O'Donnell, Christoper J.
    Orho-Melander, Marju
    Molony, Cliona M.
    Muntendam, Pieter
    Padmanabhan, Sandosh
    Palmer, Colin N. A.
    Pasko, Dorota
    Patel, Aniruddh P.
    Pedersen, Oluf
    Perola, Markus
    Peters, Annette
    Pisinger, Charlotta
    Pistis, Giorgio
    Polasek, Ozren
    Poulter, Neil
    Psaty, Bruce M.
    Rader, Daniel J.
    Rasheed, Asif
    Rauramaa, Rainer
    Reilly, Dermot F.
    Reiner, Alex P.
    Renström, Frida
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden.
    Rich, Stephen S.
    Ridker, Paul M.
    Rioux, John D.
    Robertson, Neil R.
    Roden, Dan M.
    Rotter, Jerome I.
    Rudan, Igor
    Salomaa, Veikko
    Samani, Nilesh J.
    Sanna, Serena
    Sattar, Naveed
    Schmidt, Ellen M.
    Scott, Robert A.
    Sever, Peter
    Sevilla, Raquel S.
    Shaffer, Christian M.
    Sim, Xueling
    Sivapalaratnam, Suthesh
    Small, Kerrin S.
    Smith, Albert V.
    Smith, Blair H.
    Somayajula, Sangeetha
    Southam, Lorraine
    Spector, Timothy D.
    Speliotes, Elizabeth K.
    Starr, John M.
    Stirrups, Kathleen E.
    Stitziel, Nathan
    Strauch, Konstantin
    Stringham, Heather M.
    Surendran, Praveen
    Tada, Hayato
    Tall, Alan R.
    Tang, Hua
    Tardif, Jean-Claude
    Taylor, Kent D.
    Trompet, Stella
    Tsao, Philip S.
    Tuomilehto, Jaakko
    Tybjaerg-Hansen, Anne
    van Zuydam, Natalie R.
    Varbo, Anette
    Varga, Tibor V.
    Virtamo, Jarmo
    Waldenberger, Melanie
    Wang, Nan
    Wareham, Nick J.
    Warren, Helen R.
    Weeke, Peter E.
    Weinstock, Joshua
    Wessel, Jennifer
    Wilson, James G.
    Wilson, Peter W. F.
    Xu, Ming
    Yaghootkar, Hanieh
    Young, Robin
    Zeggini, Eleftheria
    Zhang, He
    Zheng, Neil S.
    Zhang, Weihua
    Zhang, Yan
    Zhou, Wei
    Zhou, Yanhua
    Zoledziewska, Magdalena
    Howson, Joanna M. M.
    Danesh, John
    McCarthy, Mark I.
    Cowan, Chad A.
    Abecasis, Goncalo
    Deloukas, Panos
    Musunuru, Kiran
    Willer, Cristen J.
    Kathiresan, Sekar
    Exome-wide association study of plasma lipids in > 300,000 individuals2017Ingår i: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 49, nr 12, s. 1758-1766Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We screened variants on an exome-focused genotyping array in >300,000 participants (replication in >280,000 participants) and identified 444 independent variants in 250 loci significantly associated with total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-C), low-densitylipoprotein cholesterol (LDL-C), and/or triglycerides (TG). At two loci (JAK2 and A1CF), experimental analysis in mice showed lipid changes consistent with the human data. We also found that: (i) beta-thalassemia trait carriers displayed lower TC and were protected from coronary artery disease (CAD); (ii) excluding the CETP locus, there was not a predictable relationship between plasma HDL-C and risk for age-related macular degeneration; (iii) only some mechanisms of lowering LDL-C appeared to increase risk for type 2 diabetes (T2D); and (iv) TG-lowering alleles involved in hepatic production of TG-rich lipoproteins (TM6SF2 and PNPLA3) tracked with higher liver fat, higher risk for T2D, and lower risk for CAD, whereas TG-lowering alleles involved in peripheral lipolysis (LPL and ANGPTL4) had no effect on liver fat but decreased risks for both T2D and CAD.

  • 148. Liu, Gang
    et al.
    Ding, Ming
    Chiuve, Stephanie E.
    Rimm, Eric B.
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA; Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Sweden; Skåne University Hospital Malmö, Sweden.
    Meigs, James B.
    Hu, Frank B.
    Sun, Qi
    Plasma Levels of Fatty Acid-Binding Protein 4, Retinol-Binding Protein 4, High-Molecular-Weight Adiponectin, and Cardiovascular Mortality Among Men With Type 2 Diabetes A 22-Year Prospective Study2016Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 36, nr 11, s. 2259-2267Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To examine select adipokines, including fatty acid–binding protein 4, retinol-binding protein 4, and high-molecular-weight (HMW) adiponectin in relation to cardiovascular disease (CVD) mortality among patients with type 2 diabetes mellitus.

    Approach and Results: Plasma levels of fatty acid–binding protein 4, retinol-binding protein 4, and HMW adiponectin were measured in 950 men with type 2 diabetes mellitus in the Health Professionals Follow-up Study. After an average of 22 years of follow-up (1993–2015), 580 deaths occurred, of whom 220 died of CVD. After multivariate adjustment for covariates, higher levels of fatty acid–binding protein 4 were significantly associated with a higher CVD mortality: comparing extreme tertiles, the hazard ratio and 95% confidence interval of CVD mortality was 1.78 (1.22–2.59; P trend=0.001). A positive association was also observed for HMW adiponectin: the hazard ratio (95% confidence interval) was 2.07 (1.42–3.06; P trend=0.0002), comparing extreme tertiles, whereas higher retinol-binding protein 4 levels were nonsignificantly associated with a decreased CVD mortality with an hazard ratio (95% confidence interval) of 0.73 (0.50–1.07; P trend=0.09). A Mendelian randomization analysis suggested that the causal relationships of HMW adiponectin and retinol-binding protein 4 would be directionally opposite to those observed based on the biomarkers, although none of the Mendelian randomization associations achieved statistical significance.

    Conclusions: These data suggest that higher levels of fatty acid–binding protein 4 and HMW adiponectin are associated with elevated CVD mortality among men with type 2 diabetes mellitus. Biological mechanisms underlying these observations deserve elucidation, but the associations of HMW adiponectin may partially reflect altered adipose tissue functionality among patients with type 2 diabetes mellitus.

  • 149. Locke, Adam E.
    et al.
    Kahali, Bratati
    Berndt, Sonja I.
    Justice, Anne E.
    Pers, Tune H.
    Day, Felix R.
    Powell, Corey
    Vedantam, Sailaja
    Buchkovich, Martin L.
    Yang, Jian
    Croteau-Chonka, Damien C.
    Esko, Tonu
    Fall, Tove
    Ferreira, Teresa
    Gustafsson, Stefan
    Kutalik, Zoltan
    Luan, Jian'an
    Maegi, Reedik
    Randall, Joshua C.
    Winkler, Thomas W.
    Wood, Andrew R.
    Workalemahu, Tsegaselassie
    Faul, Jessica D.
    Smith, Jennifer A.
    Zhao, Jing Hua
    Zhao, Wei
    Chen, Jin
    Fehrmann, Rudolf
    Hedman, Asa K.
    Karjalainen, Juha
    Schmidt, Ellen M.
    Absher, Devin
    Amin, Najaf
    Anderson, Denise
    Beekman, Marian
    Bolton, Jennifer L.
    Bragg-Gresham, L.
    Buyske, Steven
    Demirkan, Ayse
    Deng, Guohong
    Ehret, Georg B.
    Feenstra, Bjarke
    Feitosa, Mary F.
    Fischer, Krista
    Goel, Anuj
    Gong, Jian
    Jackson, Anne U.
    Kanoni, Stavroula
    Kleber, Marcus E.
    Kristiansson, Kati
    Lim, Unhee
    Lotay, Vaneet
    Mangino, Massimo
    Leach, Irene Mateo
    Medina-Gomez, Carolina
    Medland, Sarah E.
    Nalls, Michael A.
    Palmer, Cameron D.
    Pasko, Dorota
    Pechlivanis, Sonali
    Peters, Marjolein J.
    Prokopenko, Inga
    Shungin, Dmitry
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Stancakova, Alena
    Strawbridge, Rona J.
    Sung, Yun Ju
    Tanaka, Toshiko
    Teumer, Alexander
    Trompet, Stella
    van der Laan, Sander W.
    van Settee, Jessica
    Van Vliet-Ostaptchouk, Jana V.
    Wang, Zhaoming
    Yengo, Loic
    Zhang, Weihua
    Isaacs, Aaron
    Albrecht, Eva
    Arnlov, Johan
    Arscott, Gillian M.
    Attwood, Antony P.
    Bandinelli, Stefania
    Barrett, Amy
    Bas, Isabelita N.
    Bellis, Claire
    Bennett, Amanda J.
    Berne, Christian
    Blagieva, Roza
    Blueher, Matthias
    Bohringer, Stefan
    Bonnycastle, Lori L.
    Boettcher, Yvonne
    Boyd, Heather A.
    Bruinenberg, Marcel
    Caspersen, Ida H.
    Chen, Yii-Der Ida
    Clarke, Robert
    Daw, E. Warwick
    de Craen, Anton J. M.
    Delgado, Graciela
    Dimitriou, Maria
    Doney, Alex S. F.
    Eklund, Niina
    Estrada, Karol
    Eury, Elodie
    Folkersen, Lasse
    Fraser, Ross M.
    Garcia, Melissa E.
    Geller, Frank
    Giedraitis, Vilmantas
    Gigante, Bruna
    Go, Alan S.
    Golay, Alain
    Goodall, Alison H.
    Gordon, Scott D.
    Gorski, Mathias
    Grabe, Hans-Joergen
    Grallert, Harald
    Grammer, Tanja B.
    Graessler, Jurgen
    Gronberg, Henrik
    Groves, Christopher J.
    Gusto, Gaeelle
    Haessler, Jeffrey
    Hall, Per
    Haller, Toomas
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Hartman, Catharina A.
    Hassinen, Maija
    Hayward, Caroline
    Heard-Costa, Nancy L.
    Helmer, Qinta
    Hengstenberg, Christian
    Holmen, Oddgeir
    Hottenga, Jouke-Jan
    James, Alan L.
    Jeff, Janina M.
    Johansson, Asa
    Jolley, Jennifer
    Juliusdottir, Thorhildur
    Kinnunen, Leena
    Koenig, Wolfgang
    Koskenvuo, Markku
    Kratzer, Wolfgang
    Laitinen, Jaana
    Lamina, Claudia
    Leander, Karin
    Lee, Nanette R.
    Lichtner, Peter
    Lind, Lars
    Lindstrom, Jaana
    Lo, Ken Sin
    Lobbens, Stephane
    Lorbeer, Roberto
    Lu, Yingchang
    Mach, Francois
    Magnusson, Patrik K. E.
    Mahajan, Anubha
    McArdle, Wendy L.
    McLachlan, Stela
    Menni, Cristina
    Merger, Sigrun
    Mihailov, Evelin
    Milani, Lili
    Moayyeri, Alireza
    Monda, Keri L.
    Morken, Mario A.
    Mulas, Antonella
    Mueller, Gabriele
    Mueller-Nurasyid, Martina
    Musk, Arthur W.
    Nagaraja, Ramaiah
    Noethen, Markus M.
    Nolte, Ilja M.
    Pilz, Stefan
    Rayner, Nigel W.
    Renstrom, Frida
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning. Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Rettig, Rainer
    Ried, Janina S.
    Ripke, Stephan
    Robertson, Neil R.
    Rose, Lynda M.
    Sanna, Serena
    Scharnagl, Hubert
    Scholtens, Salome
    Schumacher, Fredrick R.
    Scott, William R.
    Seufferlein, Thomas
    Shi, Jianxin
    Smith, Albert Vernon
    Smolonska, Joanna
    Stanton, Alice V.
    Steinthorsdottir, Valgerdur
    Stirrups, Kathleen
    Stringham, Heather M.
    Sundstrom, Johan
    Swertz, Morris A.
    Swift, Amy J.
    Syvanen, Ann-Christine
    Tan, Sian-Tsung
    Tayo, Bamidele O.
    Thorand, Barbara
    Thorleifsson, Gudmar
    Tyrer, Jonathan P.
    Uh, Hae-Won
    Vandenput, Liesbeth
    Verhulst, Frank C.
    Vermeulen, Sita H.
    Verweij, Niek
    Vonk, Judith M.
    Waite, Lindsay L.
    Warren, Helen R.
    Waterworth, Dawn
    Weedon, Michael N.
    Wilkens, Lynne R.
    Willenborg, Christina
    Wilsgaard, Tom
    Wojczynski, Mary K.
    Wong, Andrew
    Wrightl, Alan F.
    Zhang, Qunyuan
    Brennan, Eoin P.
    Choi, Murim
    Dastani, Zari
    Drong, Alexander W.
    Eriksson, Per
    Franco-Cereceda, Anders
    Gadin, Jesper R.
    Gharavi, Ali G.
    Goddard, Michael E.
    Handsaker, Robert E.
    Huang, Jinyan
    Karpe, Fredrik
    Kathiresan, Sekar
    Keildson, Sarah
    Kiryluk, Krzysztof
    Kubo, Michiaki
    Lee, Jong-Young
    Liang, Liming
    Lifton, Richard P.
    Ma, Baoshan
    McCarroll, Steven A.
    McKnight, Amy J.
    Min, Josine L.
    Moffatt, Miriam F.
    Montgomery, Grant W.
    Murabito, Joanne M.
    Nicholson, George
    Nyholt, Dale R.
    Okada, Yukinori
    Perry, John R. B.
    Dorajoo, Rajkumar
    Reinmaa, Eva
    Salem, Rany M.
    Sandholm, Niina
    Scott, Robert A.
    Stolk, Lisette
    Takahashi, Atsushi
    Tanaka, Toshihiro
    van 't Hooft, Ferdinand M.
    Vinkhuyzen, Anna A. E.
    Westra, Harm-Jan
    Zheng, Wei
    Zondervan, Krina T.
    Heath, Andrew C.
    Arveiler, Dominique
    Bakker, Stephan J. L.
    Beilby, John
    Bergman, Richard N.
    Blangero, John
    Bovet, Pascal
    Campbell, Harry
    Caulfield, Mark J.
    Cesana, Giancarlo
    Chakravarti, Aravinda
    Chasman, Daniel I.
    Chines, Peter S.
    Collins, Francis S.
    Crawford, Dana C.
    Cupples, L. Adrienne
    Cusi, Daniele
    Danesh, John
    de Faire, Ulf
    den Ruijter, Hester M.
    Dominiczak, Anna F.
    Erbel, Raimund
    Erdmann, Jeanette
    Eriksson, Johan G.
    Farrall, Martin
    Felix, Stephan B.
    Ferrannini, Ele
    Ferrieres, Jean
    Ford, Ian
    Forouhi, Nita G.
    Forrester, Terrence
    Franco, Oscar H.
    Gansevoort, Ron T.
    Gejman, Pablo V.
    Gieger, Christian
    Gottesman, Omri
    Gudnason, Vilmundur
    Gyllensten, Ulf
    Hall, Alistair S.
    Harris, Tamara B.
    Hattersley, Andrew T.
    Hicks, Andrew A.
    Hindorff, Lucia A.
    Hingorani, Aroon D.
    Hofman, Albert
    Homuth, Georg
    Hovingh, G. Kees
    Humphries, Steve E.
    Hunt, Steven C.
    Hypponen, Elina
    Illig, Thomas
    Jacobs, Kevin B.
    Jarvelin, Marjo-Riitta
    Joeckel, Karl-Heinz
    Johansen, Berit
    Jousilahti, Pekka
    Jukema, J. Wouter
    Jula, Antti M.
    Kaprio, Jaakko
    Kastelein, John J. P.
    Keinanen-Kiukaanniemi, Sirkka M.
    Kiemeney, Lambertus A.
    Knekt, Paul
    Kooner, Jaspal S.
    Kooperberg, Charles
    Kovacs, Peter
    Kraja, Aldi T.
    Kumari, Meena
    Kuusisto, Johanna
    Lakka, Timo A.
    Langenberg, Claudia
    Le Marchand, Laic
    Lehtimaki, Terho
    Lyssenko, Valeriya
    Mannisto, Satu
    Marette, Andre
    Matise, Tara C.
    McKenzie, Colin A.
    McKnight, Barbara
    Moll, Frans L.
    Morris, Andrew D.
    Morris, Andrew P.
    Murray, Jeffrey C.
    Nelis, Mari
    Ohlsson, Claes
    Oldehinkel, Albertine J.
    Ong, Ken K.
    Madden, Pamela A. F.
    Pasterkamp, Gerard
    Peden, John F.
    Peters, Annette
    Postma, Dirkje S.
    Pramstaller, Peter P.
    Price, Jackie F.
    Qi, Lu
    Raitakari, Olli T.
    Rankinen, Tuomo
    Rao, D. C.
    Rice, Treva K.
    Ridker, Paul M.
    Rioux, John D.
    Ritchie, Marylyn D.
    Rudan, Igor
    Salomaa, Veikko
    Samani, Nilesh J.
    Saramines, Jouko
    Sarzynski, Mark A.
    Schunkert, Heribert
    Schwarz, Peter E. H.
    Sever, Peter
    Shuldiner, Alan R.
    Sinisalo, Juha
    Stolk, Ronald P.
    Strauch, Konstantin
    Toenjes, Anke
    Tregouet, David-Alexandre
    Tremblay, Angelo
    Tremoli, Elena
    Virtamo, Jarmo
    Vohl, Marie-Claude
    Voelker, Uwe
    Waeber, Gerard
    Willemsen, Gonneke
    Witteman, Jacqueline C.
    Zillikens, M. Carola
    Adair, Linda S.
    Amouyel, Philippe
    Asselbergs, Folkert W.
    Assimes, Themistocles L.
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    Boehm, Bernhard O.
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    Bornstein, Stefan R.
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    Cauchi, Stephane
    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.
    Froguel, Philippe
    Groop, Leif C.
    Haiman, Christopher A.
    Hamsten, Anders
    Hui, Jennie
    Hunter, David J.
    Hveem, Kristian
    Kaplan, Robert C.
    Kivimaki, Mika
    Kuh, Diana
    Laakso, Markku
    Liu, Yongmei
    Martin, Nicholas G.
    Maerz, Winfried
    Melbve, Mads
    Metspalu, Andres
    Moebus, Susanne
    Munroe, Patricia B.
    Njolstad, Inger
    Oostra, Ben A.
    Palmer, Colin N. A.
    Pedersen, Nancy L.
    Perola, Markus
    Perusse, Louis
    Peters, Ulrike
    Power, Chris
    Quertermous, Thomas
    Rauramaa, Rainer
    Rivadeneira, Fernando
    Saaristo, Timo E.
    Saleheen, Danish
    Sattar, Naveed
    Schadt, Eric E.
    Schlessinger, David
    Slagboom, P. Eline
    Snieder, Harold
    Spector, Tim D.
    Thorsteinsdottir, Unnu R.
    Stumvoll, Michael
    Tuomilehto, Jaakko
    Uitterlinden, Andre G.
    Uusitupa, Matti
    van der Harst, Pim
    Walker, Mark
    Wallaschofski, Henri
    Wareham, Nicholas J.
    Watkins, Hugh
    Weir, David R.
    Wichmann, H-Erich
    Wilson, James F.
    Zanen, Pieter
    Borecki, Ingrid B.
    Deloukas, Panos
    Fox, Caroline S.
    Heid, Iris M.
    O'Connell, Jeffrey R.
    Strachan, David P.
    Stefansson, Kari
    van Duijri, Cornelia M.
    Abecasis, Goncalo R.
    Franke, Lude
    Frayling, Timothy M.
    McCarthy, Mark I.
    Visscher, Peter M.
    Scherag, Andre
    Willer, Cristen J.
    Boehnke, Michael
    Mohlke, Karen L.
    Lindgren, Cecilia M.
    Beckmann, Jacques S.
    Barroso, Ines
    North, Kari E.
    Ingelsson, Erik
    Hirschhorn, Joel N.
    Loos, Ruth J. F.
    Speliotes, Elizabeth K.
    Genetic studies of body mass index yield new insights for obesity biology2015Ingår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 518, nr 7538, s. 197-U401Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in upto 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 x 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for similar to 2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous systemin obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

  • 150. Loos, Ruth J F
    et al.
    Franks, Paul
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Francis, Richard W
    Barroso, Inês
    Gribble, Fiona M
    Savage, David B
    Ong, Ken K
    O'Rahilly, Stephen
    Wareham, Nicholas J
    TCF7L2 polymorphisms modulate proinsulin levels and beta-cell function in a British Europid population.2007Ingår i: Diabetes, ISSN 0012-1797, Vol. 56, nr 7, s. 1943-7Artikel i tidskrift (Refereegranskat)
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