Letter | Published:

New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism

Nature Genetics volume 45, pages 7682 (2013) | Download Citation

Abstract

Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood1. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits2. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.

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Acknowledgements

A complete list of acknowledgments is given in the Supplementary Note. Major funding for the research in this paper is provided by the Academy of Finland (project grants 126925, 121584, 124282, 129378 (Salve), 117787 (Gendi), 41071 (Skidi), 209072, 129255, 104781, 120315, 129269, 1114194, 206374, 251360, 139900/24300796, Center of Excellence in Complex Disease Genetics and SALVE) and Biocentrum Helsinki; Arthritis Research UK; the Augustinus Foundation; the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL); the Biomedical Research Council, Singapore (BMRC 06/1/21/19/466); BIF: Boehringer Ingelheim Fonds (travel grant to A.T.); the British Heart Foundation; the C.G. Sundell Foundation; the Canadian Institutes of Health Research (grant MOP-82893); Cancer Research UK; the Chief Scientist Office of the Scottish Government; the Children's Hospital of Philadelphia (Institute Development Award); Conselleria de Sanitat Generalitat Valenciana; the Copenhagen Graduate School of Health Sciences; the Cotswold Foundation (Research Development Award); the Curtin University and Women and Infants Research Foundation; the Danish Health Insurance Societies (Health Fund); the Danish Medical Research Council; the Danish National Research Foundation; the Danish Pediatric Asthma Centre; the Danish Pharmacists' Fund; the Danish Strategic Research Council; the Darlington Trust; the Department of Health and Social Services in Northern Ireland; Deutsche Forschungsgemeinschaft (DFG); Diabetes Hilfs- und Forschungsfonds Deutschland (DHFD; travel grant to M. Stumvoll); Diabetes UK (grants RD08/0003704 and RD08/0003692); the Dunhill Medical Trust; the Dutch Asthma Foundation (grants 3.4.01.26, 3.2.06.022, 3.4.09.081 and 3.2.10.085CO); the Dutch Ministry of the Environment (EFRE): Europäische Fonds für Regionale Entwicklung (LIFE Child Obesity); the Egmont Foundation; the Else Kröner-Fresenius Foundation; the Emil Aaltonen Foundation (T.L.); the ENGAGE project and grant agreement HEALTH-F4-2007-201413; the Erasmus Medical Center; Erasmus University, Rotterdam; the European Commission (EURO-BLCS, Beta-JUDO, Framework 5 award QLG1-CT-2000-01643, GABRIEL (Integrated Program LSH-2004-1.2.5-1 contract 018996), framework programme 6 EUROSPAN project (contract LSHG-CT-2006-018947), Sixth Research, Technological Development (RTD) Framework Programme (Contract FOOD-CT-2005-007034) and Seventh Framework Programme (FP7/2007-2013)); the European Research Council (ERC Advanced; 230374); the European Science Foundation (ESF; EU/QLRT-2001-01254); the Exeter NHS Research and Development; Faculty of Biology and Medicine of Lausanne; the Finnish Foundation of Cardiovascular Research; the Finnish Cultural Foundation; the Finnish Innovation Fund Sitra; the Finnish Ministry of Education and Culture; the Finnish Ministry of Social Affairs and Health; the Finnish Social Insurance Institution; the Foundation for Paediatric Research; Fundació La Marató de TV3; Fundación Roger Torné; Generalitat de Catalunya–Interminesterial Council for Research and Technological Innovation (CIRIT; 1999SGR) 00241; the German Diabetes Association (A.T.); the German Bundesministerium fuer Forschung und Technology (grants 01 AK 803 A-H and 01 IG 07015 G); the German Research Foundation for the Clinical Research Group Atherobesity KFO 152 (KO3512/1 to A.K.); GlaxoSmithKline; the Hagedorn Research Institute; Instituto de Salud Carlos III (CB06/02/0041, FIS PI041436, PI081151, PI041705 and PS09/00432 and FIS-FEDER 03/1615, 04/1509, 04/1112, 04/1931, 05/1079, 05/1052, 06/1213, 07/0314 and 09/02647); the Interdisciplinary Centre for Clinical Research at the University of Leipzig (B27 to A.T. and M. Stumvoll); the Integrated Research and Treatment Centre (IFB) Adiposity Diseases; the Jackstädt-Foundation; the Juho Vainio Foundation; the Juvenile Diabetes Research Foundation International (JDRF); Kuopio, Tampere and Turku University Hospital Medical Funds (grant 5031343 to T.A. Lakka and grant 9M048 to T.L.); The Lundbeck Foundation; the Lundbeck Foundation Centre of Applied Medical Genomics for Personalized Disease Prediction, Prevention and Care (LuCAMP); the March of Dimes Birth Defects Foundation (6-FY09-507); the MRC, UK (grants 74882, G0000934, G0601653, G0500539, G0600705, G0601261, G0600331, PrevMetSyn/SALVE PS0476 and MC-A760-5QX00); the Munich Center of Health Sciences (MC Health); the National Health and Medical Research Council of Australia (grants 403981 and 003209); the US National Human Genome Research Institute; the US National Institute of Allergy and Infectious Diseases; the US National Institute of Child Health and Human Development; the US National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); the US National Institutes of Health (grants U01DK062418, U01HG004423, U01HG004446, U01HG004438, R01DK075787, 1R01HD056465-01A, R01D0042157-01A, DK078150, TW05596, HL085144, HD054501, RR20649, ES10126, DK56350 and Biomedical Research Centers funding); the Netherlands Bioinformatics Centre (NBIC) BioAssist (RK/2008.024); a National Heart, Lung, and Blood Institute (NHLBI) grant 5R01HL087679-02 through the STAMPEED program (1RL1MH083268-01); the NIH Genetic Association Information Network (GAIN); the NIH/National Institute of Mental Health (NIMH) (5R01MH63706:02 and MH081802); the Rutgers University Cell and DNA Repository cooperative agreement (NIMH U24 MH068457-06); the Novo Nordisk Foundation Center for Basic Metabolic Research; the Center for Medical Systems Biology (CMSB; NWO Genomics); the Netherlands Organization for Scientific Research (NWO: Social Sciences (MaGW) and the Netherlands Organization for Health Research and Development (ZonMw) (Middelgroot-911-09-032, Spinozapremie 56-464-14192, 904-61-090, 904-61-193, 480-04-004, 400-05-717, Addiction-31160008, 985-10-002, 40-0056-98-9032 and 912-03-031); the Paavo Nurmi Foundation; the Peninsula NIHR Clinical Research Facility; the Pharmacy Foundation of 1991; the PhD School of Molecular Metabolism University of Southern Denmark; the Raine Medical Research Foundation; the Royal Society; the Sigrid Juselius Foundation; South West NHS Research and Development; the Spanish Ministry of Science and Innovation (SAF2008-00357), Turku University Hospital; the Swiss National Science Foundation (33CSCO-122661); the Tampere Tuberculosis Foundation; the Telethon Institute for Child Health Research; the Turku University Foundation; the US Centers for Disease Control and Prevention; University Hospital Oulu, Biocenter, the University of Oulu (75617); the University of Bristol; the University of Potsdam; the University of Southampton; the University of Western Australia (UWA); the VU Institute for Health and Care Research (EMGO+) and the Neuroscience Campus Amsterdam (NCA); the Wellcome Trust (grants GR069224, WT088806, 068545/Z/02, 076467, 085301, 090532, 083270, 083948, 085541/Z/08/Z, WT089549 and WT083431MA); and the Yrjö Jahnsson Foundation.

Author information

Author notes

    • Momoko Horikoshi
    • , Hanieh Yaghootkar
    •  & Dennis O Mook-Kanamori

    These authors contributed equally to this work.

    • Mark I McCarthy
    • , Struan F A Grant
    • , Vincent W V Jaddoe
    • , Marjo-Riitta Jarvelin
    • , Nicholas J Timpson
    • , Inga Prokopenko
    •  & Rachel M Freathy

    These authors jointly directed this work.

Affiliations

  1. Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.

    • Momoko Horikoshi
    • , Vasiliki Lagou
    • , Amanda J Bennett
    • , Christopher J Groves
    • , Mark I McCarthy
    •  & Inga Prokopenko
  2. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.

    • Momoko Horikoshi
    • , Anubha Mahajan
    • , Vasiliki Lagou
    • , Neil R Robertson
    • , Mark I McCarthy
    •  & Inga Prokopenko
  3. Genetics of Complex Traits, Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, UK.

    • Hanieh Yaghootkar
    • , Timothy M Frayling
    •  & Rachel M Freathy
  4. The Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands.

    • Dennis O Mook-Kanamori
    • , H Rob Taal
    • , Albert Hofman
    •  & Vincent W V Jaddoe
  5. Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.

    • Dennis O Mook-Kanamori
    • , H Rob Taal
    • , Albert Hofman
    • , Fernando Rivadeneira
    • , André G Uitterlinden
    •  & Vincent W V Jaddoe
  6. Department of Paediatrics, Erasmus Medical Center, Rotterdam, The Netherlands.

    • Dennis O Mook-Kanamori
    • , H Rob Taal
    •  & Vincent W V Jaddoe
  7. Department of Physiology and Biophysics, Weill Cornell Medical College–Qatar, Doha, Qatar.

    • Dennis O Mook-Kanamori
  8. Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.

    • Ulla Sovio
    • , Pimphen Charoen
    • , Shikta Das
    • , Sylvain Sebert
    •  & Marjo-Riitta Jarvelin
  9. Department of Medical Statistics, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK.

    • Ulla Sovio
  10. Medical Research Council (MRC) International Nutrition Group, London School of Hygiene and Tropical Medicine, London, UK.

    • Branwen J Hennig
    • , Anthony J Fulford
    •  & Andrew M Prentice
  11. MRC Keneba, Medical Research Council Laboratories, Banjul, The Gambia.

    • Branwen J Hennig
    • , Anthony J Fulford
    •  & Andrew M Prentice
  12. Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

    • Jonathan P Bradfield
    • , Haitao Zhang
    • , Hakon Hakonarson
    •  & Struan F A Grant
  13. The MRC Centre for Causal Analyses in Translational Epidemiology (CAiTE), School of Social and Community Medicine, University of Bristol, Bristol, UK.

    • Beate St Pourcain
    • , David M Evans
    • , John P Kemp
    • , George McMahon
    • , Debbie A Lawlor
    • , George Davey Smith
    • , Nicholas J Timpson
    •  & Rachel M Freathy
  14. Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

    • Pimphen Charoen
  15. Institute of Health Sciences, University of Oulu, Oulu, Finland.

    • Marika Kaakinen
    • , Sylvain Sebert
    •  & Marjo-Riitta Jarvelin
  16. Biocenter Oulu, University of Oulu, Oulu, Finland.

    • Marika Kaakinen
    •  & Marjo-Riitta Jarvelin
  17. Institute for Molecular Medicine Finland (FIMM), Helsinki University, Helsinki, Finland.

    • Diana L Cousminer
    • , Jani Heikkinen
    •  & Elisabeth Widén
  18. Department of Clinical Chemistry, University of Tampere, Tampere, Finland.

    • Terho Lehtimäki
  19. Department of Clinical Chemistry, Fimlab Laboratories, Tampere University Hospital, Tampere, Finland.

    • Terho Lehtimäki
  20. Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), The Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.

    • Eskil Kreiner-Møller
    • , Louise Pedersen
    • , Nadja Hawwa Vissing
    • , Klaus Bønnelykke
    •  & Hans Bisgaard
  21. The Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Copenhagen, Denmark.

    • Eskil Kreiner-Møller
    • , Louise Pedersen
    • , Nadja Hawwa Vissing
    • , Klaus Bønnelykke
    •  & Hans Bisgaard
  22. School of Women's and Infants' Health, The University of Western Australia, Perth, Western Australia, Australia.

    • Nicole M Warrington
    • , John P Newnham
    •  & Craig E Pennell
  23. Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.

    • Mariona Bustamante
    •  & Mònica Guxens
  24. Hospital del Mar Research Institute (IMIM), Barcelona, Spain.

    • Mariona Bustamante
    •  & Mònica Guxens
  25. Centros de Investigación Biomédica en Red Epidemiologia y Salud Pública (CIBERESP), Barcelona, Spain.

    • Mariona Bustamante
    • , Xavier Estivill
    •  & Mònica Guxens
  26. Genes and Disease Program, Centre for Genomic Regulation (CRG) and Pompeu Fabra University (UPF), Barcelona, Spain.

    • Mariona Bustamante
    •  & Xavier Estivill
  27. Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.

    • Bjarke Feenstra
    • , Frank Geller
    •  & Mads Melbye
  28. Centre for Paediatric Epidemiology and Biostatistics, MRC Centre of Epidemiology for Child Health, University College London Institute of Child Health, London, UK.

    • Diane J Berry
    • , Elina Hyppönen
    •  & Chris Power
  29. Institute of Epidemiology I, Helmholtz Zentrum Muenchen–German Research Center for Environmental Health, Munich, Germany.

    • Elisabeth Thiering
    • , Claudia Flexeder
    • , Carla M T Tiesler
    •  & Joachim Heinrich
  30. Medizinische Klinik für Nephrologie, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Berlin, Germany.

    • Thiemo Pfab
  31. Institute of Nutritional Science, University of Potsdam, Potsdam, Germany.

    • Thiemo Pfab
    •  & Berthold Hocher
  32. MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.

    • Sheila J Barton
    • , Karen A Jameson
    • , Keith M Godfrey
    • , Hazel M Inskip
    •  & Cyrus Cooper
  33. Peninsula National Institute for Health Research (NIHR) Clinical Research Facility, Peninsula College of Medicine and Dentistry, University of Exeter and Royal Devon and Exeter National Health Service (NHS) Foundation Trust, Exeter, UK.

    • Beverley M Shields
    • , Bridget A Knight
    •  & Andrew T Hattersley
  34. Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

    • Marjan Kerkhof
  35. Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.

    • Elisabeth M van Leeuwen
    • , Aaron Isaacs
    •  & Cornelia M van Duijn
  36. Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland.

    • Zoltán Kutalik
  37. Swiss Institute of Bioinformatics, Geneva, Lausanne, Basel, Bern and Zurich, Switzerland.

    • Zoltán Kutalik
  38. MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.

    • Jing Hua Zhao
    • , Marcel den Hoed
    • , Tuomas O Kilpeläinen
    • , Nicholas J Wareham
    • , Ruth J F Loos
    •  & Ken K Ong
  39. Department of Physiology, Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.

    • Virpi Lindi
    • , Tuomas O Kilpeläinen
    •  & Timo A Lakka
  40. Duke–National University of Singapore (NUS) Graduate Medical School, Singapore.

    • Liang-Kee Goh
    •  & Seang-Mei Saw
  41. Saw Swee Hock School of Public Health, NUS, Singapore.

    • Liang-Kee Goh
    •  & Seang-Mei Saw
  42. Department of Biological Psychology, Vrije Universiteit (VU) Amsterdam, Amsterdam, The Netherlands.

    • Jouke-Jan Hottenga
    • , Eco J C de Geus
    • , Jacqueline M Vink
    • , Gonneke Willemsen
    •  & Dorret I Boomsma
  43. Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA.

    • Ying Wu
    •  & Karen L Mohlke
  44. Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.

    • Olli T Raitakari
    • , Olli Simell
    •  & Maiju Saarinen
  45. Department of Clinical Physiology and Nuclear Medicine, University of Turku and Turku University Hospital, Turku, Finland.

    • Olli T Raitakari
  46. Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.

    • Marie N Harder
    • , Ehm Astrid Andersson
    • , Torben Hansen
    • , Tuomas O Kilpeläinen
    •  & Oluf Pedersen
  47. Institut de la Santé et la Recherche Médicale (INSERM) U744, Lille, France.

    • Aline Meirhaeghe
    • , Philippe Amouyel
    •  & Jean Dallongeville
  48. Institut Pasteur de Lille, Lille, France.

    • Aline Meirhaeghe
    • , Philippe Amouyel
    • , Jean Dallongeville
    •  & Philippe Froguel
  49. University Lille Nord de France, Lille, France.

    • Aline Meirhaeghe
    • , Philippe Amouyel
    • , Jean Dallongeville
    •  & Philippe Froguel
  50. Université Droit et Santé de Lille, Lille, France.

    • Aline Meirhaeghe
    • , Philippe Amouyel
    •  & Jean Dallongeville
  51. Department of Dietetics–Nutrition, Harokopio University of Athens, Athens, Greece.

    • Ioanna Ntalla
    •  & George V Dedoussis
  52. Division of Genetics, Children's Hospital, Boston, Massachusetts, USA.

    • Rany M Salem
    •  & Joel N Hirschhorn
  53. Metabolism Program, Broad Institute, Cambridge, Massachusetts, USA.

    • Rany M Salem
    •  & Joel N Hirschhorn
  54. Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.

    • Rany M Salem
    •  & Joel N Hirschhorn
  55. Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.

    • Rany M Salem
    •  & Joel N Hirschhorn
  56. Division of Endocrinology, Children's Hospital, Boston, Massachusetts, USA.

    • Rany M Salem
    •  & Joel N Hirschhorn
  57. Program in Genomics, Children's Hospital, Boston, Massachusetts, USA.

    • Rany M Salem
    •  & Joel N Hirschhorn
  58. Medical Research Institute, University of Dundee, Dundee, UK.

    • Kaixin Zhou
    •  & Ewan R Pearson
  59. Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

    • Dorota M Monies
    • , Fowzan S Alkuraya
    • , Ali Al-Odaib
    •  & Brian F Meyer
  60. Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.

    • Mirna Kirin
    •  & James F Wilson
  61. Department of Nutrition, University of North Carolina, Chapel Hill, North Carolina, USA.

    • Linda S Adair
  62. Department of Pediatrics, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.

    • Fowzan S Alkuraya
  63. Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.

    • Fowzan S Alkuraya
  64. Section of Investigative Medicine, Division of Diabetes, Endocrinology & Metabolism, Imperial College London, London, UK.

    • Alexandra I F Blakemore
    •  & Jessica L Buxton
  65. Department of Experimental and Health Science, UPF, Barcelona, Spain.

    • Xavier Estivill
  66. School of Public Health, Hammersmith Hospital, Imperial College London, London, UK.

    • Philippe Froguel
  67. NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK.

    • Keith M Godfrey
  68. INSERM U995, Faculté de Médecine, Université de Lille 2, Lille, France.

    • Frédéric Gottrand
  69. Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.

    • Torben Hansen
  70. Department of Clinical Biochemistry and Immunology, Statens Serum Institut, Copenhagen, Denmark.

    • Mads V Hollegaard
    •  & David M Hougaard
  71. Centre for Medical Systems Biology, Leiden, The Netherlands.

    • Aaron Isaacs
  72. Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark.

    • Torben Jørgensen
  73. Department of Public Health, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark.

    • Torben Jørgensen
  74. Division of Endocrinology, Diabetology and Metabolism, First Department of Pediatrics, Athens University Medical School, Aghia Sophia Children's Hospital, Athens, Greece.

    • Christina Kanaka-Gantenbein
  75. Department of Women's & Child Health, Pediatric Research Center, University of Leipzig, Leipzig, Germany.

    • Wieland Kiess
    •  & Antje Körner
  76. Research Unit of Molecular Epidemiology, Helmholtz Zentrum Muenchen–German Research Centre for Environmental Health, Munich, Germany.

    • Norman Klopp
  77. Hannover Unified Biobank, Hannover Medical School, Hannover, Germany.

    • Norman Klopp
  78. Department of Anthropology, Northwestern University, Evanston, Illinois, USA.

    • Christopher W Kuzawa
  79. Cells 2 Society: The Center for Social Disparities and Health at the Institute for Policy Research, Northwestern University, Evanston, Illinois, USA.

    • Christopher W Kuzawa
  80. Department of Pediatrics, University of Turku and Turku University Hospital, Turku, Finland.

    • Harri Niinikoski
    •  & Olli Simell
  81. Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.

    • Ben A Oostra
  82. Department of Pulmonology, Groningen Research Institute for Asthma and COPD (GRIAC), Research Institute, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

    • Dirkje S Postma
  83. School of Social and Community Medicine, University of Bristol, Bristol, UK.

    • Susan M Ring
  84. Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.

    • Fernando Rivadeneira
    •  & André G Uitterlinden
  85. Medizinische Klinik mit Schwerpunkt Nephrologie, Charité-Universitätsmedizin, Berlin, Germany.

    • Torsten Slowinski
  86. Division of Metabolic Diseases and Nutritional Medicine, Ludwig-Maximilians-University of Munich, Dr von Hauner Children's Hospital, Munich, Germany.

    • Carla M T Tiesler
  87. Department of Medicine, University of Leipzig, Leipzig, Germany.

    • Anke Tönjes
    •  & Michael Stumvoll
  88. Integrierte Forschungs- und Behandlungszentren (IFB) Adiposity Diseases, University of Leipzig, Leipzig, Germany.

    • Anke Tönjes
    • , Michael Stumvoll
    •  & Antje Körner
  89. Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark.

    • Allan Vaag
  90. Steno Diabetes Center, Gentofte, Denmark.

    • Allan Vaag
    •  & Daniel R Witte
  91. Department of Medicine, University of Turku and Turku University Hospital, Turku, Finland.

    • Jorma S Viikari
  92. Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

    • Jianhua Zhao
    • , Hakon Hakonarson
    •  & Struan F A Grant
  93. MRC Institute of Genetics and Molecular Medicine at the University of Edinburgh, Western General Hospital, Edinburgh, UK.

    • James F Wilson
  94. Institute for Sport and Health, University College Dublin, Dublin, Ireland.

    • Colin A G Boreham
  95. Obesity Prevention Program, Department of Population Medicine, Harvard Medical School/Harvard Pilgrim Health Care Institute, Boston, Massachusetts, USA.

    • Matthew W Gillman
  96. Growth, Exercise, Nutrition and Development (GENUD) Research Group, Escuela Universitaria de Ciencias de la Salud, Universidad de Zaragoza, Zaragoza, Spain.

    • Luis A Moreno
  97. Institute of Biomedical Science, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.

    • Oluf Pedersen
  98. Faculty of Health Sciences, University of Aarhus, Aarhus, Denmark.

    • Oluf Pedersen
  99. Hagedorn Research Institute, Gentofte, Denmark.

    • Oluf Pedersen
  100. Singapore Eye Research Institute, Singapore.

    • Seang-Mei Saw
  101. Kuopio Research Institute of Exercise Medicine, Kuopio, Finland.

    • Timo A Lakka
  102. Department of Medicine, Internal Medicine, Centre Hospitalier Universitaire Vaudois (CHUV) and Faculty of Biology and Medicine, Lausanne, Switzerland.

    • Peter Vollenweider
  103. Pediatric Pulmonology and Pediatric Allergology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

    • Gerard H Koppelman
  104. Human Genetics and Medical Genomics, Human Development & Health, Faculty of Medicine, University of Southampton, Southampton, UK.

    • John W Holloway
  105. Clinical & Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.

    • John W Holloway
  106. Center for Cardiovascular Research/Institute of Pharmacology, Charité, Berlin, Germany.

    • Berthold Hocher
  107. Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland.

    • Johan G Eriksson
  108. Unit of General Practice, Helsinki University Central Hospital, Helsinki, Finland.

    • Johan G Eriksson
  109. Folkhälsan Research Centre, Helsinki, Finland.

    • Johan G Eriksson
  110. Vaasa Central Hospital, Vaasa, Finland.

    • Johan G Eriksson
  111. Department of Health Promotion and Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.

    • Johan G Eriksson
    •  & Marjo-Riitta Jarvelin
  112. Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.

    • Hakon Hakonarson
    •  & Struan F A Grant
  113. Department of Lifecourse and Services, National Institute for Health and Welfare, Oulu, Finland.

    • Anneli Pouta
  114. Institute of Clinical Medicine/Obstetrics and Gynaecology, University of Oulu, Oulu, Finland.

    • Anneli Pouta
  115. Oxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford, UK.

    • Mark I McCarthy
  116. Health Protection Agency (HPA)-MRC Center, School of Public Health, Imperial College London, London, UK.

    • Marjo-Riitta Jarvelin

Consortia

  1. The Meta-Analyses of Glucose- and Insulin-related traits Consortium (MAGIC)

    A complete list of members and affiliations is provided in the Supplementary Note.

  2. Early Growth Genetics (EGG) Consortium

    A complete list of members and affiliations is provided in the Supplementary Note.

Authors

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Contributions

Discussion group (decided on analyses specific to the project): J.P.B., T.M.F., R.M.F. (co-lead/chair), S.F.A.G., M.H., V.W.V.J., M.-R.J., M.I.M., D.O.M.-K., C.E.P., I.P. (co-lead), N.J.T. and H.Y. Writing group (drafted and edited manuscript): T.M.F., R.M.F. (co-lead/chair), B.J.H., M.H. (co-lead), V.W.V.J., M.-R.J., M.I.M., D.O.M.-K., I.P., H.R.T., N.J.T. and H.Y. (co-lead). Meta-analyses and other key analyses:Stage 1, discovery meta-analysis: R.M.F. (lead), J. Heikkinen (data exchange), D.O.M.-K., I.P. and U.S. Stage 2, follow-up and overall meta-analysis: R.M.F., M.H. (co-lead), I.P. and H.Y. (co-lead). Sensitivity meta-analyses: R.M.F. and H.Y. (lead). Analyses of known type 2 diabetes, blood pressure and height loci (including ALSPAC mother-child pair analyses): R.M.F. (lead), D.A.L., N.J.T. and H.Y. Postnatal data analysis: D.L.C., R.M.F., M. Kaakinen, D.O.M.-K. (lead), E.T. and U.S. Trans-ancestry analyses and genotype risk score analysis: M.H. (lead), I.P. (chair), N.J.T., H.Y., (CHOP) J.P.B., H.H. and S.F.A.G., (CLHNS) Y.W. and K.L.M., (Generation R) H.R.T. and V.W.V.J., (MRC Keneba) B.J.H., A.J.F. and A.M.P., (SAUDI) D.O.M.-K., F.S.A. and B.F.M. and (SCORM) L.-K.G. and S.-M.S. Cohort-specific contributions:Project design: (B58C) E.H. and C.P.; (ALSPAC) D.A.L., G.D.S. and N.J.T.; (BBC) B.H. and M.I.M.; (CHOP) J.P.B., S.F.A.G., H.H. and J.Z.; (CLHNS) L.S.A. and K.L.M.; (COLAUS) P.V.; (COPSAC-2000) H.B.; (COPSAC-REGISTRY) H.B. and K.B.; (DNBC) M.M.; (EFSOCH) T.M.F. and A.T.H.; (EPIC and EPIC-Norfolk) K.K.O.; (Generation R) A.H., V.W.V.J. and D.O.M.-K.; (HBCS) J.G.E.; (HCS) C.C.; (HELENA) F. Gottrand and L.A.M.; (INMA) X.E.; (Leipzig-Kids) A.K. and W.K.; (LISAplus and GINIplus) J. Heinrich; (MRC Keneba) A.J.F., B.J.H. and A.M.P.; (NFBC1966 and NFBC1986) M.-R.J. and U.S.; (NTR) D.I.B.; (ORCADES) J.F.W.; (PANIC) T.A.L.; (PIAMA) M. Kerkhof, G.H.K. and D.S.P.; (RAINE) J.P.N. and C.E.P.; (SAUDI) F.S.A. and B.F.M.; (SCORM) L.-K.G. and S.-M.S.; (SORBS) M. Stumvoll and A.T.; (STRIP) H.N., O.T.R. and O.S.; (SWS) K.M.G. and H.M.I.; (TEENAGE) G.V.D. and I.N.; (YF) T.L. and J.S.V.; and (Young Hearts Project) C.A.G.B. Sample collection and phenotyping: (B58C) D.J.B., E.H. and C.P.; (ALSPAC) D.A.L. and G.D.S.; (BBC) B.H., T.P. and T.S.; (CHOP) H.H.; (CLHNS) L.S.A. and C.W.K.; (COLAUS) P.V.; (COPSAC-2000) H.B., L.P. and N.H.V.; (COPSAC-REGISTRY) H.B., K.B., M.V.H., D.M.H. and E.K.-M.; (DNBC) B.F., F. Geller and M.M.; (EFSOCH) A.T.H., B.A.K. and B.M.S.; (EPIC and EPIC-Norfolk) K.K.O.; (ERF) B.A.O. and C.M.v.D.; (Generation R) A.H., V.W.V.J., D.O.M.-K. and H.R.T.; (GoDARTS) E.R.P.; (HBCS) J.G.E.; (HELENA) F. Gottrand and L.A.M.; (INMA) M.G.; (Inter99) T.H., T.J., O.P., A.V. and D.R.W.; (Leipzig-Kids) A.K. and W.K.; (LISAplus and GINIplus) C.F.; (MRC Keneba) A.J.F.; (NFBC1966 and NFBC1986) M.-R.J., M. Kaakinen and A.P.; (NTR) D.I.B., E.J.C.d.G., J.M.V. and G.W.; (ORCADES) J.F.W.; (PANIC) T.O.K., T.A.L. and V. Lindi; (PIAMA) M. Kerkhof, G.H.K. and D.S.P.; (Project Viva) M.W.G.; (RAINE) J.P.N. and C.E.P.; (SAUDI) A.A.-O., B.F.M. and D.M.M.; (SCORM) L.-K.G. and S.-M.S.; (SORBS) M. Stumvoll and A.T.; (STRIP) H.N., O.T.R. and O.S.; (SWS) K.M.G.; (TEENAGE) C.K.-G. and I.N.; (YF) T.L. and J.S.V.; and (Young Hearts Project) C.A.G.B. Genotyping: (B58C and B58C-Replication) A.J.B., C.J.G., M.I.M. and N.R.R.; (ALSPAC) J.P.K., G.M. and S.M.R.; (BBC) A.J.B., B.H., M.I.M., T.P., N.R.R. and T.S.; (CHOP) S.F.A.G. and H.H.; (COPSAC-REGISTRY) M.V.H. and D.M.H.; (EFSOCH) T.M.F. and R.M.F.; (EPIC and EPIC-Norfolk) R.J.F.L., N.J.W. and K.K.O.; (ERF) B.A.O. and C.M.v.D.; (Generation R) F.R. and A.G.U.; (GoDARTS) K.Z.; (HBCS) E.W.; (HCS) J.W.H.; (HELENA) J.D. and A. Meirhaeghe; (INMA) M.B.; (Inter99) E.A.A., T.H. and M.N.H.; (Leipzig-Kids) A.K.; (LISAplus and GINIplus) N.K. and C.M.T.T.; (MRC Keneba) B.J.H.; (NFBC1966 and NFBC1986) A.I.F.B., J.L.B., P.F. and M.I.M.; (NTR) J.-J.H.; (ORCADES) J.F.W.; (PANIC) T.A.L. and V. Lindi; (PIAMA) M. Kerkhof, G.H.K. and D.S.P.; (Project Viva) J.N.H. and R.M.S.; (RAINE) J.P.N. and C.E.P.; (SAUDI) B.F.M. and D.M.M.; (SCORM) S.-M.S.; (SORBS) M. Stumvoll; (STRIP) O.T.R.; (SWS) J.W.H.; (TEENAGE) A.J.B., C.J.G., M.I.M. and N.R.R.; (YF) T.L.; and (Young Hearts Project) P.A. and A. Meirhaeghe. Statistical analysis: (B58C) D.J.B.; (B58C-Replication) M.H.; (ALSPAC) D.M.E., B.S.P. and N.J.T.; (BBC) B.H., M.H., T.P. and T.S.; (CHOP) J.P.B., S.F.A.G. and H.Z.; (CLHNS) Y.W.; (COLAUS) Z.K.; (COPSAC-2000) E.K.-M.; (COPSAC-REGISTRY) E.K.-M.; (DNBC) B.F. and F. Geller; (EFSOCH) R.M.F. and H.Y.; (EPIC and EPIC-Norfolk) M.d.H. and J.H.Z.; (ERF) A.I. and E.M.v.L.; (Generation R) D.O.M.-K. and H.R.T.; (GoDARTS) E.R.P. and K.Z.; (HBCS) D.L.C.; (HCS) K.A.J.; (HELENA) A. Meirhaeghe; (INMA) M.B.; (Inter99) E.A.A. and M.N.H.; (Leipzig-Kids) A. Mahajan; (LISAplus and GINIplus) E.T.; (MRC Keneba) A.J.F. and B.J.H.; (NFBC1966 and NFBC1986) P.C., S.D., M.H., M. Kaakinen, I.P., S.S. and U.S.; (NTR) J.-J.H.; (ORCADES) M. Kirin; (PANIC) V. Lindi; (PIAMA) M. Kerkhof; (Project Viva) M.W.G., J.N.H. and R.M.S.; (RAINE) N.M.W.; (SAUDI) D.O.M.-K.; (SCORM) L.-K.G. and S.-M.S.; (SORBS) V. Lagou and I.P.; (STRIP) O.T.R. and M. Saarinen; (SWS) S.J.B. and H.M.I.; (TEENAGE) I.N. and M.H.; (YF) D.L.C. and E.W.; and (Young Hearts Project) P.A. and A. Meirhaeghe.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Mark I McCarthy or Struan F A Grant or Vincent W V Jaddoe or Marjo-Riitta Jarvelin or Nicholas J Timpson or Inga Prokopenko or Rachel M Freathy.

Supplementary information

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    Supplementary Text and Figures

    Supplementary Figures 1–9 and Supplementary Note

Excel files

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    Supplementary Tables

    Supplementary Tables 1–13

About this article

Publication history

Received

Accepted

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DOI

https://doi.org/10.1038/ng.2477

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