Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

Journal name:
Nature Genetics
Volume:
42,
Pages:
579–589
Year published:
DOI:
doi:10.1038/ng.609
Received
Accepted
Published online
Corrected online

Abstract

By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P < 5 × 10−8. These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits.

At a glance

Figures

  1. Genome-wide Manhattan plots for the DIAGRAM+ stage 1 meta-analysis.
    Figure 1: Genome-wide Manhattan plots for the DIAGRAM+ stage 1 meta-analysis.

    Top panel summarizes the results of the unconditional meta-analysis. Previously established loci are denoted in red and loci identified by the current study are denoted in green. The ten signals in blue are those taken forward but not confirmed in stage 2 analyses. The genes used to name signals have been chosen on the basis of proximity to the index SNP and should not be presumed to indicate causality. The lower panel summarizes the results of equivalent meta-analysis after conditioning on 30 previously established and newly identified autosomal T2D-associated SNPs (denoted by the dotted lines below these loci in the upper panel). Newly discovered conditional signals (outside established loci) are denoted with an orange dot if they show suggestive levels of significance (P < 10−5), whereas secondary signals close to already confirmed T2D loci are shown in purple (P < 10−4).

  2. Regional plots of the 12 newly discovered T2D loci.
    Figure 2: Regional plots of the 12 newly discovered T2D loci.

    Genotyped and imputed SNPs passing quality control measures across all stage 1 studies are plotted with their meta-analysis P values (as −log10 values) as a function of genomic position (NCBI Build 36). In each panel, the index association SNP is represented by a diamond, with stage 1 meta-analysis results denoted by a red diamond and the combined stage 1 and stage 2 meta-analysis results denoted with a clear symbol. Estimated recombination rates (taken from HapMap CEU) are plotted to reflect the local LD structure. Color of remaining SNPs (circles) indicates LD with the index SNP according to a scale from r2 = 0 to r2 = 1 based on pairwise r2 values from HapMap CEU (red, r2 = 0.8–1.0; orange, r2 = 0.6–0.8; green, r2 = 0.4–0.6; blue, r2 = 0.2–0.4; black, r2 < 0.2; gray, no r2 value available). Gene annotations were taken from the University of California Santa Cruz genome browser.

  3. Plots of fasting blood glucose, insulin and derived indices for the established and new T2D loci.
    Figure 3: Plots of fasting blood glucose, insulin and derived indices for the established and new T2D loci.

    (a,b) Plots of fasting glucose (x axis) and fasting insulin (y axis). (c,d) Plots of HOMA-B (an index of beta cell function; x axis) and HOMA-IR (an index of insulin sensitivity; y axis). Each point refers to a single T2D association signal, with colors denoting the strength of the association to either the x-axis variable (left-hand of each pair of plots) or y-axis variable (right-hand of each pair) (red, P < 10−3; orange, 10−3 < P < 10−2; yellow, 0.01 < P < 0.05; green, 0.05 < P < 0.20; blue, P > 0.20). The two KCNQ1 associations are distinguished by the notation KCNQ1 for rs163184 and KCNQ1* for rs231362. The gene names associated with each signal have been chosen on the basis of proximity to the index SNP and should not be presumed to indicate causality.

Change history

Corrected online 27 August 2010
In the version of this article initially published, there was an error in Table 1. Specifically, for rs5945326, the risk and non-risk alleles were reversed. The correct risk allele at rs5945326 is A, the non-risk allele is G and the risk allele frequency in HapMap CEU is 0.79. These errors have been corrected in the HTML and PDF versions of the article.

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Author information

  1. These authors contributed equally.

    • Benjamin F Voight,
    • Laura J Scott,
    • Valgerdur Steinthorsdottir,
    • Andrew P Morris &
    • Christian Dina

Affiliations

  1. Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.

    • Benjamin F Voight,
    • Soumya Raychaudhuri,
    • Steve A McCarroll,
    • Ayellet V Segrè,
    • Kristin Ardlie,
    • Noisël P Burtt,
    • Gabe Crawford,
    • Amanda L Elliott,
    • Todd Green,
    • Candace Guiducci,
    • Richa Saxena,
    • Mark J Daly,
    • Jose C Florez &
    • David Altshuler
  2. Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.

    • Benjamin F Voight,
    • Soumya Raychaudhuri,
    • Ayellet V Segrè,
    • Todd Green,
    • Richa Saxena,
    • Mark J Daly,
    • Jose C Florez &
    • David Altshuler
  3. Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.

    • Benjamin F Voight,
    • Peter Shrader,
    • James B Meigs,
    • Jose C Florez &
    • David Altshuler
  4. Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.

    • Laura J Scott,
    • Cristen J Willer,
    • Martha Ganser,
    • Anne U Jackson,
    • Heather M Stringham,
    • Gonçalo R Abecasis &
    • Michael Boehnke
  5. deCODE Genetics, Reykjavik, Iceland.

    • Valgerdur Steinthorsdottir,
    • Gudmar Thorleifsson,
    • Augustine Kong,
    • G Bragi Walters,
    • Unnur Thorsteinsdottir &
    • Kari Stefansson
  6. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.

    • Andrew P Morris,
    • Eleftheria Zeggini,
    • Teresa Ferreira,
    • Katherine S Elliott,
    • Cecilia M Lindgren,
    • Inga Prokopenko,
    • N William Rayner,
    • Neil R Robertson &
    • Mark I McCarthy
  7. CNRS-UMR-8090, Institute of Biology and Lille 2 University, Pasteur Institute, Lille, France.

    • Christian Dina,
    • Christine Proença &
    • Stephane Cauchi
  8. INSERM UMR915 CNRS ERL3147, Nantes, France.

    • Christian Dina
  9. Bioinformatics Program, University of Michigan, Ann Arbor, Michigan, USA.

    • Ryan P Welch
  10. Wellcome Trust Sanger Institute, Hinxton, UK.

    • Eleftheria Zeggini,
    • Suzannah Bumpstead,
    • Felicity Payne &
    • Inês Barroso
  11. Institute of Epidemiology, Helmholtz Zentrum Muenchen, Neuherberg, Germany.

    • Cornelia Huth,
    • Harald Grallert,
    • Christian Gieger,
    • Norman Klopp,
    • Ann-Kristin Petersen,
    • Barbara Thorand,
    • H-Erich Wichmann &
    • Thomas Illig
  12. Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany.

    • Cornelia Huth,
    • Harald Grallert &
    • H-Erich Wichmann
  13. Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.

    • Yurii S Aulchenko,
    • Najaf Amin,
    • Jacqueline Witteman,
    • Albert Hofman &
    • Cornelia M van Duijn
  14. Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.

    • Laura J McCulloch,
    • Amanda J Bennett,
    • Christopher J Groves,
    • Neelam Hassanali,
    • Katharine R Owen,
    • Inga Prokopenko,
    • N William Rayner,
    • Neil R Robertson,
    • Anna L Gloyn &
    • Mark I McCarthy
  15. Ontario Institute for Cancer Research, Toronto, Ontario, Canada.

    • Guanming Wu &
    • Lincoln D Stein
  16. Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

    • Soumya Raychaudhuri
  17. Department of Molecular Biology, Harvard Medical School, Boston, Massachusetts, USA.

    • Steve A McCarroll,
    • Ayellet V Segrè,
    • Amanda L Elliott,
    • Philippe Froguel &
    • David Altshuler
  18. Medical Research Council (MRC) Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.

    • Claudia Langenberg,
    • Simon Griffin &
    • Nicholas J Wareham
  19. Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA.

    • Oliver M Hofmann &
    • Winston A Hide
  20. Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.

    • Josée Dupuis
  21. National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA.

    • Josée Dupuis &
    • Caroline S Fox
  22. Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA.

    • Lu Qi,
    • Peter Kraft,
    • Qi Sun,
    • David J Hunter &
    • Frank B Hu
  23. Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.

    • Lu Qi,
    • Peter Kraft,
    • Qi Sun,
    • David J Hunter &
    • Frank B Hu
  24. Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.

    • Lu Qi,
    • Marilyn Cornelis,
    • Rob M van Dam &
    • Frank B Hu
  25. Department of Internal Medicine, Erasmus University Medical Centre, Rotterdam, The Netherlands.

    • Mandy van Hoek,
    • Thijs van Herpt,
    • Eric Sijbrands &
    • Andre Uitterlinden
  26. MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK.

    • Pau Navarro
  27. INSERM, CESP Centre for Research in Epidemiology and Population Health, U1018, Epidemiology of Diabetes, Obesity and Chronic Kidney Disease over the Lifecourse, Villejuif, France.

    • Beverley Balkau
  28. University Paris-Sud 11, UMRS 1018, Villejuif, France.

    • Beverley Balkau
  29. Landspitali University Hospital, Reykjavik, Iceland.

    • Rafn Benediktsson &
    • Gunnar Sigurdsson
  30. Icelandic Heart Association, Kopavogur, Iceland.

    • Rafn Benediktsson &
    • Gunnar Sigurdsson
  31. Division of Endocrinology, Diabetes and Metabolism, Ulm University, Ulm, Germany.

    • Roza Blagieva &
    • Bernhard O Boehm
  32. The Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas, USA.

    • Eric Boerwinkle
  33. National Human Genome Research Institute, National Institute of Health, Bethesda, Maryland, USA.

    • Lori L Bonnycastle,
    • Peter S Chines,
    • Michael R Erdos,
    • Mario A Morken,
    • Narisu Narisu &
    • Amy J Swift
  34. Research and Development Centre, Skaraborg Primary Care, Skövde, Sweden.

    • Kristina Bengtsson Boström
  35. Department of Internal Medicine, Catharina Hospital, Eindhoven, The Netherlands.

    • Bert Bravenboer
  36. Endocrinology-Diabetology Unit, Corbeil-Essonnes Hospital, Corbeil-Essonnes, France.

    • Guillaume Charpentier
  37. Department of Biostatistics and Collaborative Studies Coordinating Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

    • David J Couper
  38. Diabetes Research Centre, Biomedical Research Institute, University of Dundee, Ninewells Hospital, Dundee, UK.

    • Alex S F Doney,
    • Andrew D Morris &
    • Colin N A Palmer
  39. Pharmacogenomics Centre, Biomedical Research Institute, University of Dundee, Ninewells Hospital, Dundee, UK.

    • Alex S F Doney,
    • Andrew D Morris &
    • Colin N A Palmer
  40. Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.

    • Amanda L Elliott,
    • Richa Saxena &
    • David Altshuler
  41. Division of Endocrinology, Diabetes, and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

    • Caroline S Fox
  42. Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.

    • Christopher S Franklin,
    • Igor Rudan,
    • Harry Campbell &
    • James F Wilson
  43. Hagedorn Research Institute, Gentofte, Denmark.

    • Niels Grarup,
    • Thomas Sparsø,
    • Torben Hansen &
    • Oluf Pedersen
  44. Centre Hospitalier Universitaire de Poitiers, Endocrinologie Diabetologie, CIC INSERM 0801, INSERM U927, Université de Poitiers, UFR, Médecine Pharmacie, Poitiers Cedex, France.

    • Samy Hadjadj
  45. Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.

    • Christian Herder &
    • Michael Roden
  46. Folkhälsan Research Center, Helsinki, Finland.

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

    • Bo Isomaa
  48. Diabetes Research and Wellness Foundation Human Islet Isolation Facility and Oxford Islet Transplant Programme, University of Oxford, Oxford, UK.

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

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

    • Torben Jørgensen
  51. Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland, USA.

    • Wen H L Kao &
    • Man Li
  52. Department of Medicine and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, Maryland, USA.

    • Wen H L Kao
  53. Department of Medicine, University of Kuopio and Kuopio University Hospital, Kuopio, Finland.

    • Johanna Kuusisto &
    • Markku Laakso
  54. Department of General Medical Practice, University of Aarhus, Aarhus, Denmark.

    • Torsten Lauritzen
  55. Department of Internal Medicine, Maxima Medical Center, Eindhoven, The Netherlands.

    • Aloysius Lieverse &
    • Thijs van Herpt
  56. Department of Clinical Sciences, Diabetes and Endocrinology Research Unit, University Hospital Malmö, Lund University, Malmö, Sweden.

    • Valeriya Lyssenko,
    • Peter Nilsson &
    • Leif Groop
  57. Department of Endocrinology, Diabetology and Nutrition, Bichat-Claude Bernard University Hospital, Assistance Publique des Hôpitaux de Paris, Paris, France.

    • Michel Marre
  58. INSERM U695, Université Paris 7, Paris, France.

    • Michel Marre
  59. Institute of Human Genetics, Helmholtz Zentrum Muenchen, Neuherberg, Germany.

    • Thomas Meitinger
  60. Institute of Human Genetics, Klinikum rechts der Isar, Technische Universität München, München, Germany.

    • Thomas Meitinger
  61. Nord-Trøndelag Health Study (HUNT) Research Center, Department of Community Medicine and General Practice, Norwegian University of Science and Technology, Trondheim, Norway.

    • Kristian Midthjell,
    • Carl Platou &
    • Kristian Hveem
  62. Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, University of Exeter, Exeter, UK.

    • John R B Perry,
    • Beverley M Shields,
    • Michael N Weedon,
    • Andrew T Hattersley &
    • Timothy M Frayling
  63. Diabetes Genetics, Institute of Biomedical and Clinical Science, Peninsula Medical School, University of Exeter, Exeter, UK.

    • John R B Perry,
    • Beverley M Shields,
    • Michael N Weedon,
    • Andrew T Hattersley &
    • Timothy M Frayling
  64. Institute of Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.

    • Wolfgang Rathmann &
    • Klaus Strassburger
  65. Department of Human Genetics, McGill University, Montreal, Canada.

    • Ghislain Rocheleau &
    • Rob Sladek
  66. Department of Medicine, Faculty of Medicine, McGill University, Montreal, Canada.

    • Ghislain Rocheleau &
    • Rob Sladek
  67. McGill University and Genome Quebec Innovation Centre, Montreal, Canada.

    • Ghislain Rocheleau &
    • Rob Sladek
  68. Department of Metabolic Diseases, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.

    • Michael Roden
  69. Department of Endocrinology and Diabetes, Norfolk and Norwich University Hospital National Health Service Trust, Norwich, UK.

    • Michael J Sampson
  70. General Medicine Division, Massachusetts General Hospital, Boston, Massachusetts, USA.

    • Peter Shrader &
    • James B Meigs
  71. Institut interrégional pour la Santé (IRSA), La Riche, France.

    • Jean Tichet
  72. Department of Medicine, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.

    • Tiinamaija Tuomi &
    • Leif Groop
  73. Department of Internal Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.

    • Timon W van Haeften
  74. Molecular Genetics, Medical Biology Section, Department of Pathology and Medical Biology, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands.

    • Jana V van Vliet-Ostaptchouk
  75. Department of Genetics, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands.

    • Cisca Wijmenga
  76. Department of Physiology and Biophysics, University of Southern California School of Medicine, Los Angeles, California, USA.

    • Richard N Bergman &
    • Richard M Watanabe
  77. National Institute of Health, Bethesda, Maryland, USA.

    • Francis S Collins
  78. Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.

    • Ulf Gyllensten
  79. University of Southern Denmark, Odense, Denmark.

    • Torben Hansen
  80. Centre for Diabetes, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

    • Graham A Hitman
  81. Department of Medicine, The Hospital of Levanger, Levanger, Norway.

    • Kristian Hveem
  82. Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA.

    • Karen L Mohlke
  83. Institute of Genetic Medicine, European Academy Bozen/Bolzano (EURAC), Bolzano, Italy.

    • Peter P Pramstaller
  84. Croatian Centre for Global Health, Faculty of Medicine, University of Split, Split, Croatia.

    • Igor Rudan
  85. Institute for Clinical Medical Research, University Hospital 'Sestre Milosrdnice', Zagreb, Croatia.

    • Igor Rudan
  86. Department of Public Health, University of Helsinki, Helsinki, Finland.

    • Jaakko Tuomilehto
  87. South Ostrobothnia Central Hospital, Seinäjoki, Finland.

    • Jaakko Tuomilehto
  88. Red RECAVA Grupo RD06/0014/0015, Hospital Universitario La Paz, Madrid, Spain.

    • Jaakko Tuomilehto
  89. Diabetes Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.

    • Mark Walker
  90. Department of Preventative Medicine, Keck Medical School, University of Southern California, Los Angeles, California, USA.

    • Richard M Watanabe
  91. Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, Minnesota, USA.

    • James S Pankow
  92. Department of Biomedical Science, Panum, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark.

    • Oluf Pedersen
  93. Faculty of Health Science, University of Aarhus, Aarhus, Denmark.

    • Oluf Pedersen
  94. Klinikum Grosshadern, Munich, Germany.

    • H-Erich Wichmann
  95. Diabetes Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

    • Jose C Florez &
    • David Altshuler
  96. Faculty of Medicine, University of Iceland, Reykjavík, Iceland.

    • Unnur Thorsteinsdottir &
    • Kari Stefansson
  97. Genomic Medicine, Imperial College London, Hammersmith Hospital, London, UK.

    • Philippe Froguel
  98. Oxford National Institute for Health Research Biomedical Research Centre, Churchill Hospital, Oxford, UK.

    • Mark I McCarthy
  99. A full list of members is provided in the Supplementary Note.

    • The MAGIC investigators &
    • The GIANT Consortium

Consortia

  1. The MAGIC investigators

  2. The GIANT Consortium

Contributions

Manuscript writing: B.F.V., L.J.S., V.S., A.P.M., C.D., E.Z., T.F., T.M.F., R. Sladek, U.T., D.A., M.B., M.I.M.

Clinical samples: A.P.M., H.G., C.L., L.Q., M.v.H., P. Navarro, K.A., B. Balkau, R. Benediktsson, R. Blagieva, L.L.B., K.B.B., B. Bravenboer, N.P.B., G. Charpentier, M.C., A.S.F.D., C.S. Fox, C. Gieger, N.G., S.G., S.H., C. Herder, B.I., T.J., P.K., J.K., T.L., A.L., V.L., M.M., T.M., K.M., P. Nilsson, K.R.O., C. Platou, W.R., M.R., M.J.S., B.M.S., G.S., T.S., K. Strassburger, Q.S., B.T., J. Tichet, T.T., R.M.v.D., T.W.v.H., T.v.H., J.V.v.V.-O., C.W., R.N.B., F.S.C., U.G., T.H., G.A.H., D.J.H., K.H., M.Laakso, K.L.M., A.D.M., C.N.A.P., P.P.P., I.R., E.S., J. Tuomilehto, M.W., N.J.W., B.O.B., H.C., A.T.H., F.B.H., J.B.M., J.S.P., O.P., T.M.F., L.G., R. Sladek, U.T., H.-E.W., J.F.W., T.I., P.F., C.M.v.D., K. Stefansson, D.A., M.B., M.I.M.

Stage 1 genotyping and analysis: B.F.V., L.J.S., V.S., A.P.M., C.D., E.Z., C. Huth, Y.S.A., G.T., T.F., H.G., N.A., C.J.W., C.L., A.V.S., M.v.H., P. Navarro, K.A., R. Benediktsson, A.J.B., L.L.B., K.B.B., S.B., N.P.B., G. Charpentier, P.S.C., M.C., G. Crawford, M.R.E., M.G., N.G., C.J.G., C. Guiducci, C. Herder, B.I., A.U.J., N.K., T.L., C.M.L., V.L., M.M., T.M., M.A.M., N.N., P. Nilsson, F.P., G.R., R. Saxena, T.S., K. Strassburger, H.M.S., A.J.S., T.T., R.M.v.D., G.B.W., J.W., R.N.B., S.C., F.S.C., U.G., K.L.M., I.R., E.S., J. Tuomilehto, A.U., N.J.W., H.C., F.B.H., T.M.F., L.G., R. Sladek, U.T., H.-E.W., J.F.W., T.I., P.F., C.M.v.D., K. Stefansson, D.A., M.B., M.I.M.

Stage 2 genotyping and analysis: B.F.V., L.J.S., V.S., A.P.M., C.D., C. Huth, Y.S.A., G.T., H.G., N.A., C.J.W., C.L., J.D., L.Q., M.v.H., P. Navarro, K.A., A.J.B., E.B., L.L.B., K.B.B., S.B., N.P.B., P.S.C., M.C., D.J.C., G. Crawford, A.S.F.D., M.R.E., C.S. Franklin, M.G., C. Gieger, N.G., S.G., C.J.G., C. Guiducci, N.H., C. Herder, B.I., A.U.J., T.J., W.H.L.K., N.K., A.K., P.K., J.K., T.L., M. Li, C.M.L., V.L., T.M., K.M., M.A.M., N.N., P. Nilsson, F.P., A.-K.P., C. Proença, I.P., W.R., N.W.R., N.R.R., G.R., M.R., M.J.S., P.S., T.S., K. Strassburger, H.M.S., Q.S., A.J.S., T.T., R.M.v.D., T.W.v.H., J.V.v.V.-O., G.B.W., M.N.W., C.W., J.W., R.N.B., S.C., F.S.C., U.G., T.H., D.J.H., K.H., M. Laakso, K.L.M., A.D.M., C.N.A.P., P.P.P., I.R., E.S., J. Tuomilehto, A.U., N.J.W., H.C., M.J.D., F.B.H., J.S.P., O.P., I.B., J.C.F., T.M.F., L.G., R. Sladek, H.-E.W., U.T., J.F.W., T.I., P.F., C.M.v.D., D.A., M.B., M.I.M.

Analysis group: B.F.V., L.J.S., V.S., A.P.M., R.P.W., C.D., E.Z., C. Huth, Y.S.A., G.T., T.F., H.G., N.A., C.J.W., J.D., M.v.H., M.G., C. Gieger, A.U.J., N.K., A.K., J.R.B.P., A.-K.P., N.W.R., N.R.R., R. Saxena, M.J.D., P.F., M.B., M.I.M.

Biological analyses: V.S., G.T., L.J.M., S.A.M., J.D., K.S.E., A.L.E., P.R.V.J., V.L., I.P., A.L.G., J.B.M., U.T., K. Stefansson, M.I.M.

Informatics analyses: B.F.V., V.S., G.W., S.R., O.M.H., A.V.S., T.G., W.A.H., L.D.S.

DIAGRAM consortium management: B.F.V., L.J.S., V.S., A.P.M., C.D., E.Z., R.N.B., S.C., F.S.C., A.H., K.L.M., E.S., J. Tuomilehto, R.M.W., G.R.A., H.C., M.J.D., A.T.H., T.M.F., L.G., R. Sladek, U.T., H.-E.W., J.F.W., T.I., P.F., C.M.v.D., K. Stefansson, D.A., M.B., M.I.M.

Competing financial interests

V.S., G.T., G.B.W, A.K., U.T. and K.S. are employed by deCODE Genetics. R.M.W. has pharmaceutical funding. 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, bioStrategies, XOMA and Daiichi-Sankyo and has been a paid invited speaker at internal scientific seminars hosted by Pfizer and Alnylam Pharmaceuticals. R.M.W. has received consulting honoraria from Merck & Co. and Vivus Inc., currently has a grant from Merck & Co. and received research material support from Takeda Pharmaceuticals North America.

Author details

Supplementary information

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  1. Supplementary Text and Figures (9M)

    Supplementary Note, Supplementary Figures 1 and 2 and Supplementary Tables 1–6

Additional data