New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk

Journal name:
Nature Genetics
Volume:
42,
Pages:
105–116
Year published:
DOI:
doi:10.1038/ng.520
Received
Accepted
Published online
Corrected online

Abstract

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

At a glance

Figures

  1. Regional plots of ten newly discovered genome-wide significant associations.
    Figure 1: Regional plots of ten newly discovered genome-wide significant associations.

    (a) ADCY5. (b) MADD. (c) ADRA2A. (d) FADS1. (e) CRY2. (f) SLC2A2. (g) GLIS3. (h) PROX1. (i) C2CD4B. (j) IGF1. For each region, directly genotyped and imputed SNPs are plotted with their meta-analysis P values (as −log10 values) as a function of genomic position (NCBI Build 35). In each panel, the stage 1 discovery SNP taken forward to stage 2 replication is represented by a blue diamond (with global meta-analysis P value), with its stage 1 discovery P value denoted by a red diamond. Estimated recombination rates (taken from HapMap) are plotted to reflect the local LD structure around the associated SNPs and their correlated proxies (according to a white-to-red scale from r2 = 0 to 1, based on pairwise r2 values from HapMap CEU). Gene annotations were taken from the UCSC genome browser.

  2. Quantile-quantile plots.
    Figure 2: Quantile-quantile plots.

    (a) Fasting glucose. (b) Beta-cell function by homeostasis model assessment (HOMA-B). (c) Fasting insulin. (d) Insulin resistance by homeostasis model assessment (HOMA-IR). In each plot, the expected null distribution is plotted along the red diagonal, the entire distribution of observed P values is plotted in black and a distribution that excludes the ten newly discovered loci shown in Figure 1 is plotted in green. For fasting glucose and HOMA-B, the distribution that excludes the four genome-wide significant fasting glucose–associated loci reported previously (in GCK, GCKR, G6PC2 and MTNR1B) is plotted in blue. A comparison of the observed P values for each trait shows that fasting glucose and HOMA-B associations are much more likely to be detected than fasting insulin and HOMA-IR associations.

  3. Variation in levels of fasting glucose depending on the number of risk alleles at newly identified loci, weighted by effect size in an aggregate genotype score for the Framingham Heart Study.
    Figure 3: Variation in levels of fasting glucose depending on the number of risk alleles at newly identified loci, weighted by effect size in an aggregate genotype score for the Framingham Heart Study.

    The bar plots show the average and standard error of fasting glucose in mmol/l for each value of the genotype score based on the regression coefficient (right y axis), and the histogram denotes the number of individuals in each genotype score category (left y axis). Comparable results were obtained for the NFBC 1966 and ARIC cohorts. On average, the range spans ~0.4 mmol/l (~7.2 mg/dl) from low to high genotype score.

Change history

Corrected online 26 March 2010
In the version of this article initially published, there were several errors in the author affiliations. These errors have been corrected in the HTML and PDF versions of the article.

References

  1. Genuth, S. et al. The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus: Follow-up report on the diagnosis of diabetes mellitus. Diabetes Care 26, 31603167 (2003).
  2. Coutinho, M., Gerstein, H.C., Wang, Y. & Yusuf, S. The relationship between glucose and incident cardiovascular events. A metaregression analysis of published data from 20 studies of 95,783 individuals followed for 12.4 years. Diabetes Care 22, 233240 (1999).
  3. Meigs, J.B., Nathan, D.M., D'Agostino, R.B. Sr. & Wilson, P.W. Fasting and postchallenge glycemia and cardiovascular disease risk: the Framingham Offspring Study. Diabetes Care 25, 18451850 (2002).
  4. UKPDS. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 352, 837853 (1998).
  5. Patel, A. et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N. Engl. J. Med. 358, 25602572 (2008).
  6. Holman, R.R., Paul, S.K., Bethel, M.A., Matthews, D.R. & Neil, H.A. 10-year follow-up of intensive glucose control in type 2 diabetes. N. Engl. J. Med. 359, 15771589 (2008).
  7. Ray, K.K. et al. Effect of intensive control of glucose on cardiovascular outcomes and death in patients with diabetes mellitus: a meta-analysis of randomised controlled trials. Lancet 373, 17651772 (2009).
  8. Prokopenko, I., McCarthy, M.I. & Lindgren, C.M. Type 2 diabetes: new genes, new understanding. Trends Genet. 24, 613621 (2008).
  9. Florez, J.C. Newly identified loci highlight beta cell dysfunction as a key cause of type 2 diabetes: Where are the insulin resistance genes? Diabetologia 51, 11001110 (2008).
  10. Weedon, M.N. et al. A common haplotype of the glucokinase gene alters fasting glucose and birth weight: association in six studies and population-genetics analyses. Am. J. Hum. Genet. 79, 9911001 (2006).
  11. Sparsø, T. et al. The GCKR rs780094 polymorphism is associated with elevated fasting serum triacylglycerol, reduced fasting and OGTT-related insulinaemia, and reduced risk of type 2 diabetes. Diabetologia 51, 7075 (2008).
  12. Orho-Melander, M. et al. A common missense variant in the glucokinase regulatory protein gene (GCKR) is associated with increased plasma triglyceride and C-reactive protein but lower fasting glucose concentrations. Diabetes 57, 31123121 (2008).
  13. Bouatia-Naji, N. et al. A polymorphism within the G6PC2 gene is associated with fasting plasma glucose levels. Science 320, 10851088 (2008).
  14. Chen, W.-M. et al. Association studies in Caucasians identify variants in the G6PC2/ABCB11 region regulating fasting glucose levels. J. Clin. Invest. 118, 26202628 (2008).
  15. Prokopenko, I. et al. Variants in MTNR1B influence fasting glucose levels. Nat. Genet. 41, 7781 (2009).
  16. Lyssenko, V. et al. Common variant in MTNR1B associated with increased risk of type 2 diabetes and impaired early insulin secretion. Nat. Genet. 41, 8288 (2009).
  17. Bouatia-Naji, N. et al. A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk. Nat. Genet. 41, 8994 (2009).
  18. Matthews, D.R. et al. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28, 412419 (1985).
  19. Pe'er, I., Yelensky, R., Altshuler, D. & Daly, M.J. Estimation of the multiple testing burden for genomewide association studies of nearly all common variants. Genet. Epidemiol. 32, 381385 (2008).
  20. Brunzell, J.D. et al. Relationships between fasting plasma glucose levels and insulin secretion during intravenous glucose tolerance tests. J. Clin. Endocrinol. Metab. 42, 222229 (1976).
  21. Weir, G.C. & Bonner-Weir, S. Five stages of evolving β-cell dysfunction during progression to diabetes. Diabetes 53, S16S21 (2004).
  22. Marchini, J., Howie, B., Myers, S., McVean, G. & Donnelly, P. A new multipoint method for genome-wide association studies by imputation of genotypes. Nat. Genet. 39, 906913 (2007).
  23. Li, Y. & Mach Abecasis, G.R. 1.0: Rapid haplotype reconstruction and missing genotype inference. Am. J. Hum. Genet. S79, 2290 (2006).
  24. Sabatti, C. et al. Genome-wide association analysis of metabolic traits in a birth cohort from a founder population. Nat. Genet. 41, 3546 (2009).
  25. Diabetes Genetics Initiative of Broad Institute of Harvard and MIT. Lund University and Novartis Institutes for BioMedical Research. Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science 316, 13311336 (2007).
  26. Ioannidis, J.P., Ntzani, E.E., Trikalinos, T.A. & Contopoulos-Ioannidis, D.G. Replication validity of genetic association studies. Nat. Genet. 29, 306309 (2001).
  27. Nejentsev, S., Walker, N., Riches, D., Egholm, M. & Todd, J.A. Rare variants of IFIH1, a gene implicated in antiviral responses, protect against type 1 diabetes. Science 324, 387389 (2009).
  28. Tirosh, A. et al. Normal fasting plasma glucose levels and type 2 diabetes in young men. N. Engl. J. Med. 353, 14541462 (2005).
  29. Saxena, R. et al. Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge. Nat. Genet. advance online publication, doi:10.1038/ng.521 (17 January 2010).
  30. Vaxillaire, M. et al. The common P446L polymorphism in GCKR inversely modulates fasting glucose and triglyceride levels and reduces type 2 diabetes risk in the DESIR prospective general French population. Diabetes 57, 22532257 (2008).
  31. Willer, C.J. et al. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat. Genet. 41, 2534 (2009).
  32. Newton-Cheh, C. et al. Eight blood pressure loci identified by genomewide association study of 34,433 people of European ancestry. Nat. Genet. 41, 666676 (2009).
  33. Aulchenko, Y.S. et al. Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts. Nat. Genet. 41, 4755 (2009).
  34. Kathiresan, S. et al. Common variants at 30 loci contribute to polygenic dyslipidemia. Nat. Genet. 41, 5665 (2009).
  35. Sunyaev, S. et al. Prediction of deleterious human alleles. Hum. Mol. Genet. 10, 591597 (2001).
  36. Thomas, P.D. et al. Applications for protein sequence-function evolution data: mRNA/protein expression analysis and coding SNP scoring tools. Nucleic Acids Res. 34, W645W650 (2006).
  37. Beer, N.L. et al. The P446L variant in GCKR associated with fasting plasma glucose and triglyceride levels exerts its effect through increased glucokinase activity in liver. Hum. Mol. Genet. 18, 40814088 (2009).
  38. Ng, P.C. & Henikoff, S. Predicting deleterious amino acid substitutions. Genome Res. 11, 863874 (2001).
  39. Schadt, E.E. et al. Mapping the genetic architecture of gene expression in human liver. PLoS Biol. 6, e107 (2008).
  40. Myers, A.J. et al. A survey of genetic human cortical gene expression. Nat. Genet. 39, 14941499 (2007).
  41. Dixon, A.L. et al. A genome-wide association study of global gene expression. Nat. Genet. 39, 12021207 (2007).
  42. Gieger, C. et al. Genetics meets metabolomics: a genome-wide association study of metabolite profiles in human serum. PLoS Genet. 4, e1000282 (2008).
  43. Schaeffer, L. et al. Common genetic variants of the FADS1 FADS2 gene cluster and their reconstructed haplotypes are associated with the fatty acid composition in phospholipids. Hum. Mol. Genet. 15, 17451756 (2006).
  44. McCarroll, S.A. et al. Integrated detection and population-genetic analysis of SNPs and copy number variation. Nat. Genet. 40, 11661174 (2008).
  45. Rung, J. et al. Genetic variant near IRS1 is associated with type 2 diabetes, insulin resistance and hyperinsulinemia. Nat. Genet. 41, 11101115 (2009).
  46. Doria, A., Patti, M.-E. & Kahn, C.R. The emerging genetic architecture of type 2 diabetes. Cell Metab. 8, 186200 (2008).
  47. Bergman, R.N. et al. Minimal model-based insulin sensitivity has greater heritability and a different genetic basis than homeostasis model assessment or fasting insulin. Diabetes 52, 21682174 (2003).
  48. Higgins, J.P. & Thompson, S.G. Quantifying heterogeneity in a metaanalysis. Stat. Med. 21, 15391558 (2002).
  49. Peter-Riesch, B., Fathi, M., Schlegel, W. & Wollheim, C.B. Glucose and carbachol generate 1,2-diacylglycerols by different mechanisms in pancreatic islets. J. Clin. Invest. 81, 11541161 (1988).
  50. Prentki, M. & Matschinsky, F.M. Ca2+, cAMP, and phospholipid-derived messengers in coupling mechanisms of insulin secretion. Physiol. Rev. 67, 11851248 (1987).
  51. Drucker, D.J. The role of gut hormones in glucose homeostasis. J. Clin. Invest. 117, 2432 (2007).
  52. Fukada, T. et al. The zinc transporter SLC39A13/ZIP13 is required for connective tissue development; its involvement in BMP/TGF-β signaling pathways. PLoS One 3, e3642 (2008).
  53. Mitro, N. et al. The nuclear receptor LXR is a glucose sensor. Nature 445, 219223 (2007).
  54. Rorsman, P. et al. Activation by adrenaline of a low-conductance G protein-dependent K+ channel in mouse pancreatic β cells. Nature 349, 7779 (1991).
  55. Keane, D. & Newsholme, P. Saturated and unsaturated (including arachidonic acid) non-esterified fatty acid modulation of insulin secretion from pancreatic β-cells. Biochem. Soc. Trans. 36, 955958 (2008).
  56. Kume, K. et al. mCRY1 and mCRY2 are essential components of the negative limb of the circadian clock feedback loop. Cell 98, 193205 (1999).
  57. Rudic, R.D. et al. BMAL1 and CLOCK, two essential components of the circadian clock, are involved in glucose homeostasis. PLoS Biol. 2, e377 (2004).
  58. Song, J.J. & Lee, Y.J. Cross-talk between JIP3 and JIP1 during glucose deprivation: SEK1–JNK2 and Akt1 act as mediators. J. Biol. Chem. 280, 2684526855 (2005).
  59. Waeber, G. et al. The gene MAPK8IP1, encoding islet-brain-1, is a candidate for type 2 diabetes. Nat. Genet. 24, 291295 (2000).
  60. Santer, R. et al. Mutations in GLUT2, the gene for the liver-type glucose transporter, in patients with Fanconi-Bickel syndrome. Nat. Genet. 17, 324326 (1997).
  61. Guillam, M.T. et al. Early diabetes and abnormal postnatal pancreatic islet development in mice lacking Glut-2. Nat. Genet. 17, 327330 (1997).
  62. Kim, Y.-S., Nakanishi, G., Lewandoski, M. & Jetten, A.M. GLIS3, a novel member of the GLIS subfamily of Kruppel-like zinc finger proteins with repressor and activation functions. Nucleic Acids Res. 31, 55135525 (2003).
  63. Senée, V. et al. Mutations in GLIS3 are responsible for a rare syndrome with neonatal diabetes mellitus and congenital hypothyroidism. Nat. Genet. 38, 682687 (2006).
  64. Song, K.-H., Li, T. & Chiang, J.Y.L. A prospero-related homeodomain protein is a novel co-regulator of hepatocyte nuclear factor 4α that regulates the cholesterol 7α-hydroxylase gene. J. Biol. Chem. 281, 1008110088 (2006).
  65. Yamagata, K. et al. Mutations in the hepatocyte nuclear factor-4α gene in maturity- onset diabetes of the young (MODY1). Nature 384, 458460 (1996).
  66. Warton, K., Foster, N.C., Gold, W.A. & Stanley, K.K. A novel gene family induced by acute inflammation in endothelial cells. Gene 342, 8595 (2004).
  67. Clemmons, D.R. Role of insulin-like growth factor in maintaining normal glucose homeostasis. Horm. Res. 62 (Suppl. 1), 7782 (2004).
  68. Servin, B. & Stephens, M. Imputation-based analysis of association studies: candidate regions and quantitative traits. PLoS Genet. 3, e114 (2007).
  69. Aulchenko, Y.S., Ripke, S., Isaacs, A. & van Duijn, C.M. GenABEL: an R library for genome-wide association analysis. Bioinformatics 23, 12941296 (2007).
  70. R Development Core Team. R: A Language and Environment for Statistical Computing (R Foundation for Statistical Computing, Vienna, 2007).
  71. Petitti, D.B. Statistical methods in meta-analysis. in Meta-analysis, Decision Analysis, and Cost-effectiveness Analysis (ed. Petitti, D.B.) 94118 (Oxford University Press, New York, 2000).
  72. Devlin, B. & Roeder, K. Genomic control for association studies. Biometrics 55, 9971004 (1999).
  73. Raychaudhuri, S. et al. Identifying relationships among genomic disease regions: predicting genes at pathogenic SNP associations and rare deletions. PLoS Genet. 5, e1000534 (2009).
  74. Lukowiak, B. et al. Identification and purification of functional human β-cells by a new specific zinc-fluorescent probe. J. Histochem. Cytochem. 49, 519528 (2001).

Download references

Author information

  1. These authors contributed equally to this work.

    • Josée Dupuis,
    • Claudia Langenberg,
    • Inga Prokopenko,
    • Richa Saxena &
    • Nicole Soranzo

Affiliations

  1. Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.

    • Josée Dupuis &
    • Alisa K Manning
  2. National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA.

    • Josée Dupuis &
    • Caroline S Fox
  3. Medical Research Council (MRC), Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.

    • Claudia Langenberg,
    • Jian'an Luan,
    • Nita G Forouhi,
    • Manjinder Sandhu,
    • Stephen J Sharp,
    • Jing Hua Zhao,
    • Ruth J F Loos &
    • Nicholas J Wareham
  4. Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.

    • Inga Prokopenko,
    • Anna L Gloyn,
    • Cecilia M Lindgren,
    • Reedik Mägi,
    • Amanda J Bennett,
    • Christopher J Groves,
    • Neelam Hassanali,
    • Paul R V Johnson,
    • Laura J McCulloch,
    • Matthew J Neville,
    • Nigel W Rayner,
    • Fredrik Karpe &
    • Mark I McCarthy
  5. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.

    • Inga Prokopenko,
    • Cecilia M Lindgren,
    • Reedik Mägi,
    • Andrew P Morris,
    • Joshua Randall,
    • Anuj Goel,
    • John F Peden,
    • Nigel W Rayner,
    • Hugh Watkins,
    • Eleftheria Zeggini &
    • Mark I McCarthy
  6. Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.

    • Richa Saxena,
    • Benjamin F Voight,
    • Amanda Elliott,
    • Steven A McCarroll,
    • Gabe Crawford,
    • Jarred B McAteer,
    • David Altshuler &
    • Jose C Florez
  7. Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.

    • Richa Saxena,
    • Benjamin F Voight,
    • Amanda Elliott,
    • Steven A McCarroll,
    • David Altshuler &
    • Jose C Florez
  8. Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.

    • Nicole Soranzo,
    • Suzannah J Bumpstead,
    • Rhian Gwilliam,
    • Naomi Hammond,
    • Simon C Potter,
    • Dhiraj Varma,
    • Eleftheria Zeggini,
    • Panos Deloukas,
    • Timothy D Spector &
    • Leena Peltonen
  9. Twin Research and Genetic Epidemiology Department, King's College London, St. Thomas' Hospital Campus, London, UK.

    • Nicole Soranzo,
    • Massimo Mangino,
    • Guangju Zhai &
    • Timothy D Spector
  10. Center for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA.

    • Anne U Jackson,
    • Heather M Stringham,
    • Xijing Han,
    • Yun Li,
    • Laura J Scott,
    • Goncalo R Abecasis &
    • Michael Boehnke
  11. Metabolic Disease Group, Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.

    • Eleanor Wheeler,
    • Felicity Payne,
    • Rosa Maria Roccasecca &
    • Inês Barroso
  12. Cardiovascular Health Research Unit and Department of Medicine, University of Washington, Seattle, Washington, USA.

    • Nicole L Glazer
  13. Centre National de la Recherche Scientifique–Unité Mixte de Recherche 8090, Pasteur Institute, Lille 2–Droit et Santé University, Lille, France.

    • Nabila Bouatia-Naji,
    • Christine Cavalcanti-Proença,
    • Amélie Bonnefond,
    • Jerome Delplanque,
    • Christian Dina,
    • Olivier Le Bacquer,
    • Cécile Lecoeur,
    • David Meyre &
    • Philippe Froguel
  14. Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.

    • Toby Johnson &
    • Sven Bergmann
  15. University Institute of Social and Preventative Medicine, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland.

    • Toby Johnson &
    • Murielle Bochud
  16. Swiss Institute of Bioinformatics, Lausanne, Switzerland.

    • Toby Johnson &
    • Sven Bergmann
  17. Department of Epidemiology and Public Health, Imperial College London, Faculty of Medicine, Norfolk Place, London, UK.

    • Paul Elliott,
    • Lachlan J M Coin,
    • Ulla Sovio &
    • Marjo-Riitta Jarvelin
  18. Boston University Data Coordinating Center, Boston, Massachusetts, USA.

    • Denis Rybin
  19. deCODE Genetics, Reykjavik, Iceland.

    • Gudmar Thorleifsson,
    • Valgerdur Steinthorsdottir,
    • G Bragi Walters,
    • Augustine Kong,
    • Unnur Thorsteinsdottir &
    • Kari Stefansson
  20. Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands.

    • Peter Henneman
  21. Institute of Epidemiology, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg, Germany.

    • Harald Grallert,
    • Christian Gieger,
    • Christa Meisinger,
    • Barbara Thorand,
    • H Erich Wichmann &
    • Thomas Illig
  22. Department of Epidemiology, Erasmus Medical College, Rotterdam, The Netherlands.

    • Abbas Dehghan,
    • Albert Hofman,
    • Fernando Rivadeneira,
    • Eric J G Sijbrands,
    • André G Uitterlinden,
    • Jaqueline C M Witteman,
    • Cornelia M van Duijn &
    • Yurii S Aulchenko
  23. Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands.

    • Jouke Jan Hottenga,
    • Eco J C de Geus,
    • Danielle Posthuma,
    • Gonneke Willemsen &
    • Dorret I Boomsma
  24. Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.

    • Christopher S Franklin,
    • Sarah H Wild,
    • Igor Rudan,
    • Harry Campbell &
    • James F Wilson
  25. MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Edinburgh, UK.

    • Pau Navarro,
    • Caroline Hayward,
    • Veronique Vitart &
    • Alan F Wright
  26. Division of Genetics, Research and Development, GlaxoSmithKline, King of Prussia, Pennsylvania, USA.

    • Kijoung Song,
    • Dawn M Waterworth &
    • Vincent Mooser
  27. Department of Cardiovascular Medicine, University of Oxford, Oxford, UK.

    • Anuj Goel,
    • John F Peden &
    • Hugh Watkins
  28. Genetics of Complex Traits, Institute of Biomedical and Clinical Sciences, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, UK.

    • John R B Perry,
    • David Melzer,
    • Michael N Weedon &
    • Timothy M Frayling
  29. National Institute of Aging, Baltimore, Maryland, USA.

    • Josephine M Egan
  30. Unit for Child and Adolescent Health and Welfare, National Institute for Health and Welfare, Biocenter Oulu, University of Oulu, Oulu, Finland.

    • Taina Lajunen
  31. Hagedorn Research Institute, Gentofte, Denmark.

    • Niels Grarup,
    • Thomas Sparsø,
    • Torben Hansen &
    • Oluf Pedersen
  32. Department of Medicine and Therapeutics, Level 7, Ninewells Hospital and Medical School, Dundee, UK.

    • Alex Doney
  33. Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.

    • Man Li &
    • W H Linda Kao
  34. Department of Nutrition–Dietetics, Harokopio University, Athens, Greece.

    • Stavroula Kanoni &
    • George V Dedoussis
  35. General Medicine Division, Massachusetts General Hospital, Boston, Massachusetts, USA.

    • Peter Shrader &
    • James B Meigs
  36. Department of Epidemiology and Public Health, University College London, London, UK.

    • Meena Kumari,
    • Eric Brunner,
    • Aroon D Hingorani,
    • Mika Kivimaki &
    • Michael Marmot
  37. Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.

    • Lu Qi &
    • Marilyn Cornelis
  38. MRC Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, UK.

    • Nicholas J Timpson,
    • Ian N M Day,
    • Debbie A Lawlor &
    • George Davey Smith
  39. Fundación para la Investigación Biomédica del Hospital Clínico San Carlos, Madrid, Spain.

    • Carina Zabena,
    • María Teresa Martínez-Larrad &
    • Manuel Serrano-Ríos
  40. Departments of Medicine and Human Genetics, McGill University, Montreal, Canada.

    • Ghislain Rocheleau &
    • Robert Sladek
  41. Genome Quebec Innovation Centre, Montreal, Canada.

    • Ghislain Rocheleau &
    • Robert Sladek
  42. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

    • Erik Ingelsson,
    • Nancy L Pedersen &
    • Patrik K E Magnusson
  43. Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.

    • Erik Ingelsson &
    • Björn Zethelius
  44. Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, USA.

    • Ping An,
    • Michael A Province &
    • Ingrid B Borecki
  45. Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA.

    • Jeffrey O'Connell,
    • Braxton D Mitchell,
    • Ruth Pakyz &
    • Alan R Shuldiner
  46. INSERM U859, Universite de Lille-Nord de France, Lille, France.

    • François Pattou
  47. Genome Technology Branch, National Human Genome Research Institute, Bethesda, Maryland, USA.

    • Praveen Sethupathy,
    • Lori L Bonnycastle,
    • Peter Chines,
    • Michael R Erdos,
    • Mario A Morken,
    • Narisu Narisu,
    • Daniel Pearson,
    • Amy Swift,
    • Francis S Collins &
    • David Schlessinger
  48. The Broad Institute, Cambridge, Massachusetts, USA.

    • Kristin Ardlie &
    • Leena Peltonen
  49. Leiden Genome Technology Center, Leiden University Medical Center, Leiden, The Netherlands.

    • Yavuz Ariyurek
  50. INSERM U780, Paris Sud University, Villejuif, France.

    • Beverley Balkau
  51. The Heart Research Institute, Sydney, New South Wales, Australia.

    • Philip Barter
  52. PathWest Laboratory of Western Australia, Department of Molecular Genetics, J Block, QEII Medical Centre, Nedlands West Australia, Australia.

    • John P Beilby &
    • Jennie Hui
  53. School of Surgery and Pathology, University of Western Australia, Nedlands West Australia, Australia.

    • John P Beilby
  54. Department of Social Medicine, University of Bristol, Bristol, UK.

    • Yoav Ben-Shlomo
  55. Landspitali University Hospital, Reykjavik, Iceland.

    • Rafn Benediktsson &
    • Gunnar Sigurðsson
  56. Icelandic Heart Association, Kopavogur, Iceland.

    • Rafn Benediktsson &
    • Gunnar Sigurðsson
  57. The Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas, USA.

    • Eric Boerwinkle
  58. Steno Diabetes Center, Gentofte, Denmark.

    • Knut Borch-Johnsen
  59. Faculty of Health Science, University of Aarhus, Aarhus, Denmark.

    • Knut Borch-Johnsen &
    • Oluf Pedersen
  60. Department of Medicine, University of Leipzig, Leipzig, Germany.

    • Yvonne Böttcher,
    • Anke Tönjes &
    • Michael Stumvoll
  61. Endocrinology–Diabetology Unit, Corbeil-Essonnes Hospital, Essonnes, France.

    • Guillaume Charpentier
  62. Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.

    • Yii-Der Ida Chen,
    • Mark O Goodarzi &
    • Jerome I Rotter
  63. Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Oxford, UK.

    • Robert Clarke
  64. Centre for Genetic Epidemiology and Biostatistics, University of Western Australia, Perth, Australia.

    • Matthew N Cooper,
    • Annette C Fedson,
    • Laila Simpson,
    • Kim L Ward &
    • Lyle J Palmer
  65. Istituto di Neurogenetica e Neurofarmacologia (INN), Consiglio Nazionale delle Ricerche, c/o Cittadella Universitaria di Monserrato, Monserrato, Cagliari, Italy.

    • Laura Crisponi,
    • Silvia Naitza,
    • Marco Orrù,
    • Serena Sanna,
    • Antonio Cao,
    • Angelo Scuteri &
    • Manuela Uda
  66. Western Australian Sleep Disorders Research Institute, Queen Elizabeth Medical Centre II, Perth, Australia.

    • Annette C Fedson,
    • David R Hillman,
    • Sutapa Mukherjee,
    • Laila Simpson,
    • Kim L Ward &
    • Lyle J Palmer
  67. Department of Endocrinology, Diabetes and Nutrition, Charite-Universitaetsmedizin Berlin, Berlin, Germany.

    • Antje Fischer-Rosinsky,
    • Andreas F H Pfeiffer &
    • Joachim Spranger
  68. Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.

    • Antje Fischer-Rosinsky,
    • Andreas F H Pfeiffer &
    • Joachim Spranger
  69. Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

    • Caroline S Fox &
    • Gordon H Williams
  70. Department of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands.

    • Rune Frants &
    • Ko Willems van Dijk
  71. Department of Cardiovascular Research, Istituto di Ricerche Farmacologiche 'Mario Negri', Milan, Italy.

    • Maria Grazia Franzosi
  72. Institut National de la Santé et de la Recherche Médicale, Institut National de la Recherche Agronomique, Université Paris 13, Bobigny Cedex, France.

    • Pilar Galan
  73. Department of Medicine III, Division Prevention and Care of Diabetes, University of Dresden, Dresden, Germany.

    • Jürgen Graessler,
    • Stefan R Bornstein &
    • Peter Schwarz
  74. Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

    • Scott Grundy
  75. Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.

    • Ulf Gyllensten
  76. Centre Hospitalier Universitaire, de Poitiers, Endocrinologie Diabetologie, CIC INSERM 0802, INSERM U927, Université de Poitiers, Unité de Formation et de Recherche, Médecine Pharmacie, Poitiers, France.

    • Samy Hadjadj
  77. Department of Public Health and Clinical Medicine, Section for Nutritional Research, Umeå University, Umeå, Sweden.

    • Göran Hallmans
  78. Department of Clinical Sciences, Obstetrics and Gynecology, University of Oulu, Oulu, Finland.

    • Anna-Liisa Hartikainen
  79. Centre National de Génotypage/Institut de génomique/Commissariat á l'énergie atomique, Evry Cedex, France.

    • Simon C Heath,
    • G Mark Lathrop &
    • Diana Zelenika
  80. INSERM U872, Faculté de Médecine Paris Descartes, Paris Cedex, France.

    • Serge Hercberg &
    • Pierre Meneton
  81. Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.

    • Christian Herder &
    • Michael Roden
  82. Institute of Genetic Medicine, European Academy Bozen/Bolzano (EURAC), Viale Druso, Bolzano, Italy, Affiliated Institute of the University Lübeck, Lübeck, Germany.

    • Andrew A Hicks,
    • Cristian Pattaro,
    • Irene Pichler &
    • Peter Paul Pramstaller
  83. Department of Pulmonary Physiology, Sir Charles Gairdner Hospital, Perth, Australia.

    • David R Hillman &
    • Sutapa Mukherjee
  84. Busselton Population Medical Research Foundation, Sir Charles Gairdner Hospital, Perth, Australia.

    • Jennie Hui &
    • Lyle J Palmer
  85. Heart Institute of Western Australia, Sir Charles Gairdner Hospital, Nedlands West Australia, Australia.

    • Joe Hung
  86. School of Medicine and Pharmacology, University of Western Australia, Nedlands West Australia, Australia.

    • Joe Hung
  87. Folkhalsan Research Centre, Helsinki, Finland.

    • Bo Isomaa &
    • Tiinamaija Tuomi
  88. Malmska Municipal Health Care Center and Hospital, Jakobstad, Finland.

    • Bo Isomaa
  89. Nuffield Department of Surgery, University of Oxford, Oxford, UK.

    • Paul R V Johnson
  90. Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark.

    • Torben Jørgensen
  91. Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark.

    • Torben Jørgensen
  92. National Institute for Health and Welfare, Unit of Population Studies, Turku, Finland.

    • Antti Jula
  93. Institute of Health Sciences and Biocenter Oulu, University of Oulu, Oulu, Finland.

    • Marika Kaakinen &
    • Marjo-Riitta Jarvelin
  94. Department of Public Health, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

    • Jaakko Kaprio &
    • Jaakko Tuomilehto
  95. National Institute for Health and Welfare, Unit for Child and Adolescent Mental Health, Helsinki, Finland.

    • Jaakko Kaprio
  96. Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.

    • Jaakko Kaprio,
    • Markus Perola,
    • Samuli Ripatti,
    • Peter J Wagner,
    • Kaisa Silander &
    • Leena Peltonen
  97. Department of Internal Medicine and Biocenter Oulu, Oulu, Finland.

    • Y Antero Kesaniemi
  98. Diabetes Genetics, Institute of Biomedical and Clinical Science, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, UK.

    • Beatrice Knight,
    • Beverley Shields &
    • Andrew T Hattersley
  99. National Institute for Health and Welfare, Unit of Living Conditions, Health and Wellbeing, Helsinki, Finland.

    • Seppo Koskinen
  100. Interdisciplinary Centre for Clinical Research, University of Leipzig, Leipzig, Germany.

    • Peter Kovacs
  101. The Danish Twin Registry, Epidemiology, Institute of Public Health, University of Southern Denmark, Odense, Denmark.

    • Kirsten Ohm Kyvik
  102. Department of Clinical Sciences, Diabetes and Endocrinology, Lund University, University Hospital Malmö, Malmö, Sweden.

    • Valeriya Lyssenko &
    • Leif Groop
  103. Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, California, USA.

    • Robert Mahley
  104. Diabetes Research Center, Diabetes Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

    • Jarred B McAteer,
    • David M Nathan,
    • David Altshuler &
    • Jose C Florez
  105. Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.

    • Jarred B McAteer,
    • David M Nathan,
    • Gordon H Williams,
    • David Altshuler,
    • James B Meigs &
    • Jose C Florez
  106. Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.

    • Ruth McPherson
  107. Oxford National Institute for Health Research, Biomedical Research Centre, Churchill Hospital, Oxford, UK.

    • Matthew J Neville,
    • Fredrik Karpe &
    • Mark I McCarthy
  108. Department of Clinical Genetics, Erasmus Medical College, Rotterdam, The Netherlands.

    • Ben A Oostra
  109. Biomedical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK.

    • Colin N A Palmer &
    • Andrew D Morris
  110. Department of Geriatric Medicine and Metabolic Disease, Second University of Naples, Naples, Italy.

    • Giuseppe Paolisso
  111. National Institute for Health and Welfare, Unit of Public Health Genomics, Helsinki, Finland.

    • Markus Perola,
    • Samuli Ripatti,
    • Peter J Wagner,
    • Kaisa Silander &
    • Leena Peltonen
  112. Department of Medical Genetics, University of Helsinki, Helsinki, Finland.

    • Markus Perola &
    • Leena Peltonen
  113. Department of Medical Statistics, Epidemiology and Medical Informatics, Andrija Stampar School of Public Health, Medical School, University of Zagreb, Rockefellerova, Zagreb, Croatia.

    • Ozren Polasek
  114. Department of Clinical Genetics, VU University and Medical Center, Amsterdam, The Netherlands.

    • Danielle Posthuma
  115. Department of Obstetrics and Gynaecology, Oulu University Hospital, Oulu, Finland.

    • Anneli Pouta
  116. Departments of Medicine, Epidemiology and Health Services, University of Washington, Seattle, Washington, USA.

    • Bruce M Psaty
  117. Group Health Research Institute, Group Health Cooperative, Seattle, Washington, USA.

    • Bruce M Psaty
  118. Institute of Biometrics and Epidemiology, German Diabetes Centre, Leibniz Centre at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.

    • Wolfgang Rathmann
  119. Department of Biostatistics, University of Washington, Seattle, Washington, USA.

    • Kenneth Rice
  120. Department of Internal Medicine, Erasmus Medical College, Rotterdam, The Netherlands.

    • Fernando Rivadeneira,
    • Eric J G Sijbrands,
    • André G Uitterlinden,
    • Mandy van Hoek &
    • M Carola Zillikens
  121. Department of Metabolic Diseases, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.

    • Michael Roden
  122. Department of Public Health and Clinical Medicine, Section for Family Medicine, Umeå University, Umeå, Sweden.

    • Olov Rolandsson
  123. School of Public Health, Department of General Practice, University of Aarhus, Aarhus, Denmark.

    • Annelli Sandbaek
  124. Department of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge, Cambridge, UK.

    • Manjinder Sandhu
  125. MRC Epidemiology Resource Centre, University of Southampton, Southampton General Hospital, Southampton, UK.

    • Avan Aihie Sayer,
    • Holly Syddall &
    • Cyrus Cooper
  126. Department of Epidemiology, University of Texas, M.D. Anderson Cancer Center, Houston, Texas, USA.

    • Paul Scheet
  127. Leibniz-Institut für Arterioskleroseforschung an der Universität Münster, Münster, Germany.

    • Udo Seedorf
  128. Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.

    • Anders Hamsten on behalf of Procardis Consortium &
    • Angela Silveira
  129. Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA.

    • Andrew Singleton
  130. Department of Epidemiology, University of Washington, Seattle, Washington, USA.

    • Nicholas L Smith
  131. Seattle Epidemiologic Research and Information Center, Department of Veterans Affairs Office of Research and Development, Seattle, Washington, USA.

    • Nicholas L Smith
  132. Department of Medical Sciences, Uppsala University, Uppsala, Sweden.

    • Ann-Christine Syvänen &
    • Lars Lind
  133. Medstar Research Institute, Baltimore, Maryland, USA.

    • Toshiko Tanaka
  134. Clinical Research Branch, National Institute on Aging, Baltimore, Maryland, USA.

    • Toshiko Tanaka
  135. Institut interrégional pour la santé (IRSA), La Riche, France.

    • Jean Tichet
  136. Coordination Centre for Clinical Trials, University of Leipzig, Leipzig, Germany.

    • Anke Tönjes
  137. Department of Medicine, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.

    • Tiinamaija Tuomi
  138. Department of Internal Medicine, Leiden University Medical Centre, Leiden, The Netherlands.

    • Ko Willems van Dijk
  139. Research Unit, Cardiovascular Genetics, Nancy University Henri Poincaré, Nancy, France.

    • Sophie Visvikis-Siest
  140. EMGO Institute for Health and Care Research, Department of Psychiatry, VU University Medical Center, Amsterdam, The Netherlands.

    • Nicole Vogelzangs &
    • Brenda W J H Penninx
  141. Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.

    • Gérard Waeber &
    • Peter Vollenweider
  142. Genomic Medicine, Imperial College London, Hammersmith Hospital, London, UK.

    • Andrew Walley &
    • Philippe Froguel
  143. Epidemiology and Public Health, Queen's University Belfast, Belfast, UK.

    • John W G Yarnell
  144. Medical Products Agency, Uppsala, Sweden.

    • Björn Zethelius
  145. See Supplementary Note for a full list of authors.

    • DIAGRAM Consortium,
    • GIANT Consortium &
    • Global BPgen Consortium
  146. National Institute for Health and Welfare, Unit of Chronic Disease Epidemiology and Prevention, Helsinki, Finland.

    • Veikko Salomaa
  147. Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.

    • Frank B Hu
  148. Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.

    • Frank B Hu
  149. Genetic Epidemiology and Clinical Research Group, Department of Public Health and Clinical Medicine, Section for Medicine, Umeå University Hospital, Umeå, Sweden.

    • Paul W Franks
  150. London School of Hygiene and Tropical Medicine, London, UK.

    • Shah Ebrahim
  151. Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.

    • W H Linda Kao
  152. The Welch Center for Prevention, Epidemiology, and Clinical Research, School of Medicine and Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.

    • W H Linda Kao
  153. Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA.

    • James S Pankow
  154. Department of Endocrinology and Diabetes, Norfolk and Norwich University Hospital National Health Service Trust, Norwich, UK.

    • Michael J Sampson
  155. Department of Medicine, University of Kuopio and Kuopio University Hospital, Kuopio, Finland.

    • Johanna Kuusisto &
    • Markku Laakso
  156. Faculty of Health Science, University of Southern Denmark, Odense, Denmark.

    • Torben Hansen
  157. Institute of Biomedical Science, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark.

    • Oluf Pedersen
  158. Department of Neurology, General Central Hospital, Bolzano, Italy.

    • Peter Paul Pramstaller
  159. Department of Neurology, University of Lübeck, Lübeck, Germany.

    • Peter Paul Pramstaller
  160. Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany.

    • H Erich Wichmann
  161. Klinikum Grosshadern, Munich, Germany.

    • H Erich Wichmann
  162. School of Medicine, University of Split, Split, Croatia.

    • Igor Rudan
  163. Gen-Info Ltd., Zagreb, Croatia.

    • Igor Rudan
  164. Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

    • Richard N Bergman,
    • Thomas A Buchanan &
    • Richard M Watanabe
  165. Department of Medicine, Division of Endocrinology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

    • Thomas A Buchanan
  166. Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA.

    • Karen L Mohlke
  167. National Institute for Health and Welfare, Unit of Diabetes Prevention, Helsinki, Finland.

    • Jaakko Tuomilehto &
    • Timo T Valle
  168. South Ostrobothnia Central Hospital, Seinajoki, Finland.

    • Jaakko Tuomilehto
  169. Departments of Medicine and Epidemiology, University of Washington, Seattle, Washington, USA.

    • David S Siscovick
  170. Longitudinal Studies Section, Clinical Research Branch, National Institute on Aging, NIH, Baltimore, Maryland, USA.

    • Luigi Ferrucci
  171. Faculty of Medicine, University of Iceland, Reykjavík, Iceland.

    • Unnur Thorsteinsdottir &
    • Kari Stefansson
  172. Lab of Cardiovascular Sciences, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.

    • Angelo Scuteri
  173. Department of Clinical Sciences/Clinical Chemistry, University of Oulu, Oulu, Finland.

    • Aimo Ruokonen
  174. National Institute of Health and Welfare, Oulu, Finland.

    • Marjo-Riitta Jarvelin
  175. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

    • Richard M Watanabe
  176. MRC–Health Protection Agency Centre for Environment and Health, Imperial College London, London, UK.

    • Paul Elliott

Consortia

  1. DIAGRAM Consortium

  2. GIANT Consortium

  3. Global BPgen Consortium

  4. Anders Hamsten on behalf of Procardis Consortium

  5. the MAGIC investigators

    • Richard N Bergman,
    • Thomas A Buchanan,
    • Francis S Collins,
    • Karen L Mohlke,
    • Jaakko Tuomilehto,
    • Timo T Valle,
    • David Altshuler,
    • Jerome I Rotter,
    • David S Siscovick,
    • Brenda W J H Penninx,
    • Dorret I Boomsma,
    • Panos Deloukas,
    • Timothy D Spector,
    • Timothy M Frayling,
    • Luigi Ferrucci,
    • Augustine Kong,
    • Unnur Thorsteinsdottir,
    • Kari Stefansson,
    • Cornelia M van Duijn,
    • Yurii S Aulchenko,
    • Antonio Cao,
    • Angelo Scuteri,
    • David Schlessinger,
    • Manuela Uda,
    • Aimo Ruokonen,
    • Marjo-Riitta Jarvelin,
    • Dawn M Waterworth,
    • Peter Vollenweider,
    • Leena Peltonen,
    • Vincent Mooser,
    • Goncalo R Abecasis,
    • Nicholas J Wareham,
    • Robert Sladek,
    • Philippe Froguel,
    • Richard M Watanabe,
    • James B Meigs,
    • Leif Groop,
    • Michael Boehnke,
    • Mark I McCarthy,
    • Jose C Florez &
    • Inês Barroso

Contributions

A full list of Author Contributions appears in the Supplementary Note.

Competing financial interests

J.B.M. currently has research grants from GlaxoSmithKline and Sanofi-Aventis, and serves on consultancy boards for Eli Lilly and Interleukin Genetics. J.C.F. has received consulting honoraria from Merck, Pfizer, bioStrategies, XOMA and Publicis Healthcare Communications Group, a global advertising agency engaged by Amylin Pharmaceuticals. deCODE authors are employees at deCODE genetics and own stock or stock options in the company. P.W.F. has received consulting honoraria from Unilever. P.V. and G.W. received financial support from GlaxoSmithKline to build the CoLaus study. V.M., K.S. and D.M.W. are all full-time employees at GlaxoSmithKline. I.B. and spouse own stock in GlaxoSmithKline and Incyte.

Corresponding authors

Correspondence to:

Author details

Supplementary information

PDF files

  1. Supplementary Text and Figures (1M)

    Supplementary Note, Supplementary Tables 2–4 and Supplementary Figures 1–4

Excel files

  1. Supplementary Table 1 (164K)

    Study characteristics for discovery (a) and replication (b) cohorts

Additional data