Article | Published:

Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes

Nature Genetics volume 44, pages 981990 (2012) | Download Citation

Abstract

To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip, including 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two showing sex-differentiated association. Genome-wide analyses of these data are consistent with a long tail of additional common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signaling and cell cycle regulation, in diabetes pathogenesis.

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Acknowledgements

Funding for this study was provided by the Academy of Finland (77299, 102318, 110413, 118065, 123885, 124243, 129680, 129293, 129494, 136895, 139635, 141005, 213506 and 251217); Agence Nationale de la Recherche (France); the American Diabetes Association (7-08-MN-OK); Association Française des Diabétiques; Association de Langue Française pour l'Etude du Diabète et des Maladies Métaboliques (France); Association Diabète Risque Vasculaire (France); British Diabetic Association (BDA) Research (UK); the British Heart Foundation (RG/98002 and RG2008/08); Cancer Research UK; the Central Norway Health Authority; the Central Finland Hospital District; the Center for Inherited Disease Research (CIDR) (USA); the Chief Scientist Office, Scotland (CZB/4/672); the City of Kuopio (Finland); the City of Leutkirch (Germany); the Department of Health (UK); Deutsche Forschungsgemeinschaft (ER1 55/6-2); Diabetes UK; the Doris Duke Charitable Foundation (USA); the Estonian government (SF0180142s0); the European Commission: ENGAGE (HEALTH-F4-2007- 201413), EXGENESIS (LSHM-CT-2004-005272), 245536, QLG1-CT-2002-00896 and 2004310; the European Commission (Marie Curie: FP7-PEOPLE-2010-IEF); the European Regional Development Fund; the Faculty of Medicine at the Norwegian University of Science and Technology; the Finnish Diabetes Association; the Finnish Diabetes Research Foundation; the Finnish Foundation for Cardiovascular Research; the Finnish Heart Association; the Finnish Medical Society; the Folkhälsan Research Foundation (Finland); the Food Standards Agency (UK); the Foundation for Life and Health in Finland; the Federal Ministry of Education and Research (BMBF) (Germany); the Federal Ministry of Health (Germany); the General Secretary of Research and Technology (Greece); the German Center for Diabetes Research (DZD); the German Research Council (GRK 1041); the Great Wine Estates of the Margaret River region of Western Australia; Groupe d'Etude des Maladies Métaboliques et Systémiques (France); Harvard Medical School (USA); the Heinz Nixdorf Foundation (Germany); Helmholtz Zentrum München–Research Center for Environment and Health (Germany); the Helsinki University Central Hospital Research Foundation (Finland); IngaBritt and Arne Lundberg's Research Foundation (Sweden) (grant 359); the Ministry of Health (Ricerca Corrente) (Italy); Karolinska Institutet (Sweden); the Knut and Alice Wallenberg Foundation (Sweden) (KAW 2009.0243); Kuopio University Hospital (Finland); the Municipal Heath Care Center and Hospital, Jakobstad, Finland; the Ministry of Social Affairs and Health (Finland); the Ministry of Education and Culture (Finland) (627; 2004–2011); the Ministry of Innovation, Science, Research and Technology of North Rhine-Westphalia (Germany); the Medical Research Council (UK) (G0000649 and G0601261); an MRC-GSK pilot programme grant (UK); the Munich Center of Health Sciences (MC Health) (Germany); the National Genome Research Network (NGFN) (Germany); the National Heart, Lung, and Blood Institute (NHLBI) (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367, R01HL086694, N01HC25195 and N02HL64278); the National Human Genome Research Institute (NHGRI) (U01HG004402 and N01HG65403); the US National Institutes of Health (USA) (HHSN268200625226C, UL1RR025005, U01HG004399, 1R21NS064908, 1Z01HG000024, AG028555, AG08724, AG04563, AG10175, AG08861 and CA055075); the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (DK062370, DK058845, DK072193, DK078616, DK080140 and DK073490); the Närpes Health Care Foundation (Finland); the National Health Screening Service of Norway; the National Institute of Health Research (UK); the National Institute for Health and Welfare (Finland); the Nord-Trøndelag County Council (Norway); the Nordic Center of Excellence in Disease Genetics; the Norwegian Institute of Public Health; the Norwegian Research Council; Novo Nordisk Fonden (Denmark); the Ollqvist Foundation (Sweden); the Oxford NIHR Biomedical Research Centre (UK); the Paavo Nurmi Foundation (Finland); the Päivikki and Sakari Sohlberg Foundation (Finland); the Perklén Foundation (Sweden); Pfizer; the Pirkanmaa Hospital District (Finland); Programme National de Recherche sur le Diabète (France); Programme Hospitalier de Recherche Clinique (French Ministry of Health); the Region of Nord-Pas-de-Calais (Contrat de Projets Etat-Région) (France); Research into Ageing (UK); the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center; the Royal Swedish Academy of Sciences; Sarstedt AG & Co. (Germany); the Signe and Ane Gyllenberg Foundation (Sweden); the Slottery Machine Association (Finland); the Social Insurance Institution of Finland (4/26/2010); the South OstroBothnia Hospital District (Finland); the State of Baden-Württemberg, Germany; the Stockholm County Council (560183 and 562183); Stroke Association (UK); the Swedish Research Council (8691, 09533, 2009-1039, Dnr 521-2010-3490, Dnr 521-2007-4037, Dnr 521-2008-2974, Dnr 825-2010-5983 and Dnr 349-2008-6589); the Swedish Cultural Foundation in Finland; the Swedish Diabetes Foundation; the Swedish Heart-Lung Foundation; the Swedish Foundation for Strategic Research; the Swedish Society of Medicine; the Swedish Research Council; the Swedish Research Council for Infrastructures; The Sigrid Juselius Foundation (Finland); the Torsten and Ragnar Söderberg Foundation (Sweden) (MT33/09); University Hospital Essen (Germany); University of Tromsø (Norway); Uppsala University (Sweden); Uppsala University Hospital (Sweden); and the Wellcome Trust (GR072960, 076113, 077016, 081682, 083948, 083270, 084711, 086596, 090367, 090532 and 098051). A more detailed set of acknowledgments is provided in the Supplementary Note.

Author information

Author notes

    • Leena Peltonen

    Deceased.

    • Andrew P Morris
    • , Benjamin F Voight
    • , Tanya M Teslovich
    • , Teresa Ferreira
    •  & Ayellet V Segrè

    These authors contributed equally to this work.

    • David Altshuler
    • , Michael Boehnke
    •  & Mark I McCarthy

    These authors jointly directed this work.

Affiliations

  1. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.

    • Andrew P Morris
    • , Teresa Ferreira
    • , Anubha Mahajan
    • , Inga Prokopenko
    • , Ashish Kumar
    • , Vasiliki Lagou
    • , Cecilia M Lindgren
    • , N William Rayner
    • , Steven Wiltshire
    • , Antigone S Dimas
    • , John R B Perry
    • , Neil Robertson
    • , Ghazala Mirza
    • , Joseph Trakalo
    • , Peter J Donnelly
    •  & Mark I McCarthy
  2. Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA.

    • Benjamin F Voight
    • , Ayellet V Segrè
    • , Elizabeth J Rossin
    • , Soumya Raychaudhuri
    • , Pierre Fontanillas
    • , Noël Burtt
    • , Jason Carey
    • , Andrew T Crenshaw
    • , George B Grant
    • , Candace Guiducci
    • , Melissa Parkin
    • , Wendy Winckler
    • , Sekar Kathiresan
    •  & David Altshuler
  3. Department of Pharmacology, University of Pennsylvania–Perelman School of Medicine, Philadelphia, Pennsylvania, USA.

    • Benjamin F Voight
  4. Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.

    • Tanya M Teslovich
    • , Hyun Min Kang
    • , Laura J Scott
    • , Heather M Stringham
    • , Anne U Jackson
    • , Goncalo R Abecasis
    •  & Michael Boehnke
  5. Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.

    • Ayellet V Segrè
    • , Elizabeth J Rossin
    • , Jose C Florez
    • , Sekar Kathiresan
    •  & David Altshuler
  6. Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.

    • Ayellet V Segrè
    • , Jose C Florez
    • , James B Meigs
    •  & David Altshuler
  7. deCODE Genetics, Reykjavik, Iceland.

    • Valgerdur Steinthorsdottir
    • , Augustine Kong
    • , Gudmar Thorleifsson
    • , Unnur Thorsteinsdottir
    •  & Kari Stefansson
  8. Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.

    • Rona J Strawbridge
    • , Karl Gertow
    • , Bengt Sennblad
    • , Angela Silveira
    •  & Anders Hamsten
  9. Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden.

    • Rona J Strawbridge
    • , Karl Gertow
    • , Bengt Sennblad
    • , Angela Silveira
    •  & Anders Hamsten
  10. Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.

    • Hassan Khan
    • , Kay-Tee Khaw
    • , Danish Saleheen
    •  & John Danesh
  11. Research Unit of Molecular Epidemiology, Helmholtz Zentrum Muenchen, Neuherberg, Germany.

    • Harald Grallert
    • , Norman Klopp
    •  & Thomas Illig
  12. Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.

    • Inga Prokopenko
    • , N William Rayner
    • , Neil Robertson
    • , Christopher J Groves
    • , Katharine R Owen
    •  & Mark I McCarthy
  13. Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR) 1087, Nantes, France.

    • Christian Dina
  14. Centre National de la Recherche Scientifique (CNRS) UMR 6291, Nantes, France.

    • Christian Dina
  15. Department of Biology, Medicine and Health, Nantes University, Nantes, France.

    • Christian Dina
  16. Estonian Genome Center, University of Tartu, Tartu, Estonia.

    • Tonu Esko
    • , Krista Fischer
    • , Kaarel Krjutškov
    •  & Andres Metspalu
  17. Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.

    • Tonu Esko
    •  & Andres Metspalu
  18. Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.

    • Ross M Fraser
    • , Harry Campbell
    • , Jackie F Price
    •  & James F Wilson
  19. Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.

    • Stavroula Kanoni
    • , Sarah E Hunt
    • , Simon Potter
    • , Kathleen Stirrups
    • , Sarah Edkins
    • , Cordelia Langford
    • , Eleftheria Zeggini
    • , Ines Barroso
    • , Samuli Ripatti
    •  & Panos Deloukas
  20. Medical Research Council (MRC) Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.

    • Claudia Langenberg
    • , Jian'an Luan
    • , Ruth J F Loos
    • , Nita G Forouhi
    •  & Nicholas J Wareham
  21. Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany.

    • Martina Müller-Nurasyid
  22. Institute of Genetic Epidemiology, Helmholtz Zentrum Muenchen, Neuherberg, Germany.

    • Martina Müller-Nurasyid
    • , Julia Meyer
    •  & Christian Gieger
  23. Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-Universität, Munich, Germany.

    • Martina Müller-Nurasyid
  24. Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, University Duisburg-Essen, Essen, Germany.

    • Sonali Pechlivanis
    • , Karl-Heinz Jöckel
    •  & Susanne Moebus
  25. CNRS UMR 8199, Institute of Biology and Lille 2 University, Pasteur Institute, Lille, France.

    • Loic Yengo
    • , Elodie Eury
    • , Stéphane Lobbens
    • , Stephane Cauchi
    •  & Philippe Froguel
  26. Laboratory of Mathematics, CNRS UMR 8524, University Lille 1, Model for Data Analysis and Learning (MODAL) Team, Institut National de Recherche en Informatique et en Automatique (INRIA) Lille Nord-Europe, Lille, France.

    • Loic Yengo
  27. Diabetes Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland.

    • Leena Kinnunen
    •  & Jaakko Tuomilehto
  28. Health Science and Technology MD Program, Harvard University and Massachusetts Institute of Technology, Boston, Massachusetts, USA.

    • Elizabeth J Rossin
  29. Harvard Biological and Biomedical Sciences Program, Harvard University, Boston, Massachusetts, USA.

    • Elizabeth J Rossin
  30. Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

    • Soumya Raychaudhuri
  31. Partners Center for Personalized Genomic Medicine, Boston, Massachusetts, USA.

    • Soumya Raychaudhuri
  32. National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA.

    • Andrew D Johnson
    • , Caroline Fox
    •  & Josée Dupuis
  33. Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.

    • Antigone S Dimas
  34. Biomedical Sciences Research Center Al Fleming, Vari, Greece.

    • Antigone S Dimas
  35. Charles R Bronfman Institute for Personalized Medicine, Mount Sinai School of Medicine, New York, New York, USA.

    • Ruth J F Loos
  36. Child Health and Development Institute, Mount Sinai School of Medicine, New York, New York, USA.

    • Ruth J F Loos
  37. Department of Preventive Medicine, Mount Sinai School of Medicine, New York, New York, USA.

    • Ruth J F Loos
  38. Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.

    • Sailaja Vedantam
    •  & Jose C Florez
  39. Division of Genetics and Endocrinology, Children's Hospital, Boston, Massachusetts, USA.

    • Sailaja Vedantam
  40. Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.

    • Han Chen
    • , Ching-Ti Liu
    •  & Josée Dupuis
  41. Diabetes Research Center, Diabetes Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

    • Jose C Florez
  42. Division of Endocrinology and Metabolism, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.

    • Caroline Fox
  43. Boston University Data Coordinating Center, Boston, Massachusetts, USA.

    • Denis Rybin
  44. Collaborative Studies Coordinating Center, Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

    • David J Couper
  45. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.

    • Wen Hong L Kao
    •  & Man Li
  46. Department of Nutrition and Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.

    • Marilyn C Cornelis
    • , Peter Kraft
    • , Qi Sun
    • , Rob M van Dam
    • , David J Hunter
    • , Lu Qi
    •  & Frank Hu
  47. Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.

    • Peter Kraft
    •  & David J Hunter
  48. Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.

    • Qi Sun
    • , David J Hunter
    • , Lu Qi
    •  & Frank Hu
  49. Saw Swee Hock School of Public Health, National University of Singapore, Singapore.

    • Rob M van Dam
  50. National Human Genome Research Institute, US National Institutes of Health, Bethesda, Maryland, USA.

    • Peter S Chines
    • , Lori L Bonnycastle
    •  & Francis S Collins
  51. Nord-Trondelag Health Study (HUNT) Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway.

    • Oddgeir L Holmen
    • , Carl G P Platou
    •  & Kristian Hveem
  52. Centre for Genetic Epidemiology and Biostatistics, The University of Western Australia, Nedlands, Western Australia, Australia.

    • Robert Lawrence
  53. Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, University of Exeter, Exeter, UK.

    • John R B Perry
    • , Andrew R Wood
    •  & Timothy M Frayling
  54. Department of Internal Medicine, Levanger Hospital, Nord-Trøndelag Health Trust, Levanger, Norway.

    • Carl G P Platou
  55. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

    • Emil Rehnberg
    • , Nancy L Pedersen
    •  & Erik Ingelsson
  56. Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

    • Suthesh Sivapalaratnam
    • , Mieke D Trip
    •  & Kees Hovingh
  57. Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.

    • Alena Stančáková
    • , Markku Laakso
    •  & Johanna Kuusisto
  58. Institute for Molecular Medicine Finland (FIMM), Helsinki, Finland.

    • Emmi Tikkanen
    •  & Samuli Ripatti
  59. Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.

    • Emmi Tikkanen
    • , Satu Männistö
    • , Johan G Eriksson
    • , Samuli Ripatti
    •  & Veikko Salomaa
  60. Department of Clinical Science Malmö, Lund University Diabetes Centre, Scania University Hospital, Lund University, Malmö, Sweden.

    • Peter Almgren
    • , Mozhgan Dorkhan
    • , Anna Jonsson
    • , Jasmina Kravic
    • , Eero Lindholm
    • , Valeriya Lyssenko
    • , Olle Melander
    • , Peter M Nilsson
    •  & Leif C Groop
  61. Institute of Biomedicine, Physiology, University of Eastern Finland, Kuopio, Finland.

    • Mustafa Atalay
    •  & Timo A Lakka
  62. Faculty of Medicine, University of Iceland, Reykjavík, Iceland.

    • Rafn Benediktsson
    • , Unnur Thorsteinsdottir
    •  & Kari Stefansson
  63. Department of Endocrinology and Metabolism, Landspitali University Hospital, Reykjavík, Iceland.

    • Rafn Benediktsson
    • , Astradur B Hreidarsson
    •  & Gunnar Sigurðsson
  64. Endocrinology-Diabetology Unit, Corbeil-Essonnes Hospital, Corbeil-Essonnes, France.

    • Guillaume Charpentier
  65. Diabetes Research Centre, Biomedical Research Institute, University of Dundee, Ninewells Hospital, Dundee, UK.

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

    • Alex S F Doney
    • , Colin N A Palmer
    •  & Andrew D Morris
  67. Icelandic Heart Association, Kopavogur, Iceland.

    • Valur Emilsson
    •  & Gunnar Sigurðsson
  68. Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland.

    • Tom Forsen
    •  & Johan G Eriksson
  69. Vaasa Health Care Centre, Vaasa, Finland.

    • Tom Forsen
  70. Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

    • Bruna Gigante
    • , Karin Leander
    •  & Ulf de Faire
  71. Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.

    • Christian Herder
    •  & Michael Roden
  72. Busselton Population Medical Research Institute, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.

    • Jennie Hui
    • , Alan James
    • , Bill Musk
    •  & John Beilby
  73. PathWest Laboratory Medicine of Western Australia, Queen Elizabeth II Medical Centre, Nedlands, Western Australia, Australia.

    • Jennie Hui
    •  & John Beilby
  74. School of Pathology and Laboratory Medicine, The University of Western Australia, Nedlands, Western Australia, Australia.

    • Jennie Hui
    •  & John Beilby
  75. School of Population Health, The University of Western Australia, Nedlands, Western Australia, Australia.

    • Jennie Hui
    •  & Bill Musk
  76. Department of Pulmonary Physiology and Sleep Medicine, West Australian Sleep Disorders Research Institute, Queen Elizabeth II Medical Centre, Nedlands, Western Australia, Australia.

    • Alan James
  77. School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia, Australia.

    • Alan James
    •  & Bill Musk
  78. Institute of Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.

    • Wolfgang Rathmann
  79. Institute of Human Genetics, University of Bonn, Bonn, Germany.

    • Thomas W Mühleisen
    •  & Markus M Nöthen
  80. Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.

    • Thomas W Mühleisen
    •  & Markus M Nöthen
  81. Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.

    • Bill Musk
  82. Department of Cardiology, University General Hospital Attikon, Athens, Greece.

    • Loukianos Rallidis
  83. South Karelia Central Hospital, Lappeenranta, Finland.

    • Jouko Saramies
  84. Department of Genetics, Evolution and Environment, University College London (UCL) Genetics Institute, University College London, London, UK.

    • Sonia Shah
    •  & Delilah Zabaneh
  85. Department of Clinical Chemistry and Central Laboratory, University of Ulm, Ulm, Germany.

    • Gerald Steinbach
    •  & Roman Wennauer
  86. Institute of Epidemiology II, Helmholtz Zentrum Muenchen, Neuherberg, Germany.

    • Barbara Thorand
    •  & Annette Peters
  87. Centro Cardiologico Monzino, IRCCS, Milan, Italy.

    • Fabrizio Veglia
    • , Damiano Baldassarre
    •  & Elena Tremoli
  88. MRC Institute of Genetics and Molecular Medicine at the University of Edinburgh, Western General Hospital, Edinburgh, UK.

    • Harry Campbell
    •  & James F Wilson
  89. Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.

    • Cornelia van Duijn
    • , Andre G Uitterlinden
    •  & Albert Hofman
  90. Netherland Genomics Initiative, Netherlands Consortium for Healthy Ageing and Centre for Medical Systems Biology, Rotterdam, The Netherlands.

    • Cornelia van Duijn
    •  & Andre G Uitterlinden
  91. Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.

    • Andre G Uitterlinden
    •  & Eric Sijbrands
  92. Oxford National Institute for Health Research Biomedical Research Centre, Churchill Hospital, Oxford, UK.

    • Katharine R Owen
    •  & Mark I McCarthy
  93. Molecular Medicine, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.

    • Ann-Christine Syvänen
  94. Unit of General Practice, Helsinki University General Hospital, Helsinki, Finland.

    • Johan G Eriksson
  95. Folkhälsan Research Center, Helsinki, Finland.

    • Johan G Eriksson
    • , Tiinamaija Tuomi
    •  & Bo Isomaa
  96. INSERM CESP U1018, Villejuif, France.

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

    • Beverley Balkau
  98. Department of Medicine, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.

    • Tiinamaija Tuomi
  99. Department of Social Services and Health Care, Jakobstad, Finland.

    • Bo Isomaa
  100. Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA.

    • Alan R Shuldiner
  101. Geriatric Research Education and Clinical Center, Baltimore Veterans Administration Medical Center, Baltimore, Maryland, USA.

    • Alan R Shuldiner
  102. Program in Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.

    • Alan R Shuldiner
  103. Department of Medicine/Metabolic Diseases, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.

    • Michael Roden
  104. University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.

    • Ines Barroso
  105. National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.

    • Ines Barroso
  106. Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.

    • Tom Wilsgaard
    •  & Inger Njølstad
  107. Kuopio Research Institute of Exercise Medicine, Kuopio, Finland.

    • Rainer Rauramaa
    •  & Timo A Lakka
  108. Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland.

    • Rainer Rauramaa
  109. Department of Medical Sciences, Uppsala University, Akademiska Sjukhuset, Uppsala, Sweden.

    • Lars Lind
  110. Department of Dietetics-Nutrition, Harokopio University, Athens, Greece.

    • George Dedoussis
  111. Faculty of Medicine, Institute of Health Sciences, University of Oulu, Oulu, Finland.

    • Sirkka M Keinanen-Kiukaanniemi
  112. Unit of General Practice, Oulu University Hospital, Oulu, Finland.

    • Sirkka M Keinanen-Kiukaanniemi
  113. Finnish Diabetes Association, Tampere, Finland.

    • Timo E Saaristo
  114. Pirkanmaa Hospital District, Tampere, Finland.

    • Timo E Saaristo
  115. Department of Internal Medicine, South Ostrobothnia Central Hospital, Seinäjoki, Finland.

    • Eeva Korpi-Hyövälti
    •  & Jaakko Tuomilehto
  116. Department of Medicine, Central Finland Central Hospital, Jyväskylä, Finland.

    • Juha Saltevo
  117. Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

    • Karen L Mohlke
  118. Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.

    • Richard N Bergman
  119. Red RECAVA Grupo RD06/0014/0015, Hospital Universitario La Paz, Madrid, Spain.

    • Jaakko Tuomilehto
  120. Centre for Vascular Prevention, Danube-University Krems, Krems, Austria.

    • Jaakko Tuomilehto
  121. Division of Endocrinology and Diabetes, Department of Internal Medicine, University Medical Centre Ulm, Ulm, Germany.

    • Bernhard O Boehm
  122. Genomic Medicine, Imperial College London, Hammersmith Hospital, London, UK.

    • Philippe Froguel
  123. Department of Pharmacological Sciences, University of Milan, Milan, Italy.

    • Damiano Baldassarre
    •  & Elena Tremoli
  124. Institute of Cardiovascular Science, University College London, London, UK.

    • Steve E Humphries
  125. Center for Non-Communicable Diseases Pakistan, Karachi, Pakistan.

    • Danish Saleheen
  126. Clinic of Cardiology, West German Heart Centre, University Hospital of Essen, University Duisburg-Essen, Essen, Germany.

    • Raimund Erbel
  127. Hannover Unified Biobank, Hannover Medical School, Hannover, Germany.

    • Thomas Illig
  128. Department of Statistics, University of Oxford, Oxford, UK.

    • Peter J Donnelly
  129. Diabetes Genetics, Institute of Biomedical and Clinical Science, Peninsula Medical School, University of Exeter, Exeter, UK.

    • Andrew T Hattersley
  130. Human Genetics Center, University of Texas Health Science Center at Houston, Houston, Texas, USA.

    • Eric Boerwinkle
  131. Human Genome Sequencing Center at Baylor College of Medicine, Houston, Texas, USA.

    • Eric Boerwinkle
  132. Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.

    • Sekar Kathiresan
  133. Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, Minnesota, USA.

    • James S Pankow
  134. General Medicine Division, Massachusetts General Hospital, Boston, Massachusetts, USA.

    • James B Meigs
  135. Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.

    • David Altshuler
  136. Department of Molecular Biology, Harvard Medical School, Boston, Massachusetts, USA.

    • David Altshuler
  137. Diabetes Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

    • David Altshuler

Consortia

  1. the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium

    Wellcome Trust Case Control Consortium

    Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) Investigators

    Genetic Investigation of ANthropometric Traits (GIANT) Consortium

    Asian Genetic Epidemiology Network–Type 2 Diabetes (AGEN-T2D) Consortium

    South Asian Type 2 Diabetes (SAT2D) Consortium

Authors

    Contributions

    Writing group: A.P.M., B.F.V., T.M.T., T. Ferreira, A.V.S., V. Steinthorsdottir, R.J.S., H.K., H.G., A. Mahajan, I.P., M.B. and M.I.M.

    Competing interests

    V.S., G.T., U.T. and K.S. are employees at deCODE genetics, a biotechnology company that provides genetic testing services, and own stock and/or stock options in the company. J.F. received consulting honoraria from Novartis, Eli Lilly and Pfizer. I.B. and spouse own stock in GlaxoSmithKline and Incyte.

    Corresponding authors

    Correspondence to Andrew P Morris or Michael Boehnke or Mark I McCarthy.

    Supplementary information

    PDF files

    1. 1.

      Supplementary Text and Figures

      Supplementary Note, Supplementary Figures 1–13 and Supplementary Tables 1 and 3–16

    Excel files

    1. 1.

      Supplementary Table 2

      Summary of combined meta-analysis for 65 novel and established T2D susceptibility loci

    About this article

    Publication history

    Received

    Accepted

    Published

    DOI

    https://doi.org/10.1038/ng.2383

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