Article | Published:

Seventy-five genetic loci influencing the human red blood cell

Nature volume 492, pages 369375 (20 December 2012) | Download Citation

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Abstract

Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10−8, which together explain 4–9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.

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Change history

  • 19 December 2012

    Footnote symbols in the Table 1 legend were corrected.

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Data deposits

Summary statistics from the genome-wide association study are available from the European Genome‐Phenome Archive (EGA, http://www.ebi.ac.uk/ ega) under accession number EGAS00000000132.

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Acknowledgements

A detailed list of acknowledgements is provided in the Supplementary Material.

Author information

Author notes

    • Pim van der Harst
    • , Weihua Zhang
    • , Irene Mateo Leach
    • , Augusto Rendon
    • , Niek Verweij
    • , Joban Sehmi
    • , Dirk S. Paul
    • , Ulrich Elling
    • , Andrew A. Hicks
    • , Josef Martin Penninger
    • , Christian Gieger
    • , Jaspal S. Kooner
    • , Willem H. Ouwehand
    • , Nicole Soranzo
    •  & John C. Chambers

    These authors contributed equally to this work.

Affiliations

  1. Department of Cardiology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands.

    • Pim van der Harst
    • , Irene Mateo Leach
    • , Niek Verweij
    • , Rudolf A. de Boer
    • , Herman H. W. Silljé
    • , Wiek H. van Gilst
    •  & Dirk J. van Veldhuisen
  2. Department of Genetics, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands.

    • Pim van der Harst
    • , Lude Franke
    •  & Harm-Jan Westra
  3. Department of Epidemiology and Biostatistics, Imperial College London, London W2 1PG, UK.

    • Weihua Zhang
    • , Abtehale Al-Hussani
    • , Paul F. O’Reilly
    • , Paul Elliott
    • , Marjo-Riitta Jarvelin
    •  & John C. Chambers
  4. Ealing Hospital NHS Trust, Middlesex UB1 3HW, UK.

    • Weihua Zhang
    • , Joban Sehmi
    • , Sian-Tsung Tan
    • , Kathy Miller
    • , Jaspal S. Kooner
    •  & John C. Chambers
  5. Department of Haematology, University of Cambridge, Cambridge CB2 0XY, UK.

    • Augusto Rendon
    • , Aparna Radhakrishnan
    • , Katrin Voss
    • , Cornelis A. Albers
    • , Antony Attwood
    • , Stephen F. Garner
    • , Jennifer Jolley
    • , Heather Lloyd-Jones
    • , Stuart Meacham
    • , Jennifer Sambrook
    • , Jonathan Stephens
    •  & Willem H. Ouwehand
  6. NHS Blood and Transplant, Cambridge CB2 0PT, UK.

    • Augusto Rendon
    • , Aparna Radhakrishnan
    • , Katrin Voss
    • , Cornelis A. Albers
    • , Antony Attwood
    • , Stephen F. Garner
    • , Jennifer Jolley
    • , Heather Lloyd-Jones
    • , Stuart Meacham
    • , Jennifer Sambrook
    • , Jonathan Stephens
    •  & Willem H. Ouwehand
  7. MRC Biostatistics Unit, Institute of Public Health, Cambridge CB2 2SR, UK.

    • Augusto Rendon
  8. NIHR Cambridge Biomedical Research Centre, Cambridge CB2 0QQ, UK.

    • Augusto Rendon
    • , Aparna Radhakrishnan
    • , Katrin Voss
    • , Antony Attwood
    • , Stephen F. Garner
    • , Jennifer Jolley
    • , Heather Lloyd-Jones
    • , Stuart Meacham
    • , Jennifer Sambrook
    • , Jonathan Stephens
    •  & Willem H. Ouwehand
  9. National Heart and Lung Institute, Imperial College London, London W12 0NN, UK.

    • Joban Sehmi
    • , Sian-Tsung Tan
    • , William O. Cookson
    • , Miriam F. Moffatt
    • , James Scott
    •  & Jaspal S. Kooner
  10. Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.

    • Dirk S. Paul
    • , Aparna Radhakrishnan
    • , Cornelis A. Albers
    • , Stavroula Kanoni
    • , So-Youn Shin
    • , Antony Attwood
    • , Stuart Meacham
    • , Yasin Memari
    • , Ramiro Ramirez-Solis
    • , Panos Deloukas
    • , Willem H. Ouwehand
    •  & Nicole Soranzo
  11. Institute of Molecular Biotechnology of the Austrian Academy of Sciences, 1030 Vienna, Austria.

    • Ulrich Elling
    • , Maria Novatchkova
    • , Ursula Puc
    • , Gerald Wirnsberger
    •  & Josef Martin Penninger
  12. Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, California 90033, USA.

    • Hooman Allayee
    •  & Jaana Hartiala
  13. Institute of Clinical Sciences, Imperial College London, London W12 0NN, UK.

    • Xinzhong Li
  14. NIHR Cardiovascular Biomedical Research Unit, Royal Brompton and Harefield NHS Foundation Trust and Imperial College London, London SW3 6NP, UK.

    • Xinzhong Li
    •  & John C. Chambers
  15. Center for Biomedicine, European Academy Bozen/Bolzano (EURAC), 39100 Bolzano, Italy.

    • Christian X. Weichenberger
    • , Martin Gögele
    • , Francisco S. Domingues
    • , Aude Saint-Pierre
    • , Peter P. Pramstaller
    •  & Andrew A. Hicks
  16. Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, 3508 Utrecht, The Netherlands.

    • Folkert W. Asselbergs
    •  & Vinicius Tragante
  17. Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, 3508 Utrecht, The Netherlands.

    • Folkert W. Asselbergs
    • , Paul I. W. de Bakker
    •  & Ale Algra
  18. Department of Medical Genetics, Biomedical Genetics, University Medical Center Utrecht, 3508 Utrecht, The Netherlands.

    • Folkert W. Asselbergs
    •  & Paul I. W. de Bakker
  19. Institute of Genetics and Biophysics “Adriano Buzzati-Traverso”-CNR, 80131 Naples, Italy.

    • Marina Ciullo
    • , Evelin Mihailov
    • , Teresa Nutile
    • , Daniela Ruggiero
    •  & Rossella Sorice
  20. Clinica Pediatrica 2a, Dipartimento di Scienze Biomediche e Biotecnologie - Università di Cagliari, Ospedale Regionale Microcitemie ASL8, 09121 Cagliari, Italy.

    • Fabrice Danjou
    • , Franco Anni
    •  & Renzo Galanello
  21. Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR) 1087, BP 70721 44007 Nantes cedex, 1 Nantes, France.

    • Christian Dina
  22. Centre National de la Recherche Scientifique (CNRS) UMR 6291, BP 70721 44007 Nantes cedex 1, Nantes, France

    • Christian Dina
  23. School of Medecine, Nantes University, 44000 Nantes, France.

    • Christian Dina
  24. Estonian Genome Center of University of Tartu, 51010 Tartu, Estonia.

    • Tõnu Esko
    • , Krista Fischer
    •  & Andres Metspalu
  25. Institute of Molecular and Cell Biology, University of Tartu, 51010 Tartu, Estonia.

    • Tõnu Esko
    •  & Andres Metspalu
  26. MRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol BS8 2BN, UK.

    • David M. Evans
    • , John P. Kemp
    •  & George Davey Smith
  27. Department of Medical Genetics, University of Lausanne, CH-1005 Lausanne, Switzerland.

    • Micha Hersch
    •  & Jacques S. Beckmann
  28. Swiss Institute of Bioinformatics, CH-1015 Lausanne, Switzerland.

    • Micha Hersch
  29. deCODE genetics, 101 Reykjavik, Iceland.

    • Hilma Holm
    • , Daniel Fannar Gudbjartsson
    • , Patrick Sulem
    • , Unnur Thorsteinsdottir
    •  & Kari Stefansson
  30. Department of Biological Psychology, VU University, 1081 BT Amsterdam, The Netherlands.

    • Jouke-Jan Hottenga
    • , Abdel Abdellaoui
    • , Eco J. C. de Geus
    • , Marleen H. de Moor
    • , Gonneke Willemsen
    •  & Dorret I. Boomsma
  31. Mannheim Institute of Public Health, Social and Preventive Medicine, Medical Faculty of Mannheim, University of Heidelberg, D-68167 Mannheim, Germany.

    • Marcus E. Kleber
    • , Bernd Genser
    •  & Winfried Maerz
  32. LURIC Study nonprofit LLC, D-79098 Freiburg, Germany.

    • Marcus E. Kleber
  33. Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford OX3 7LJ, UK.

    • Vasiliki Lagou
    •  & Inga Prokopenko
  34. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.

    • Vasiliki Lagou
    •  & Inga Prokopenko
  35. MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UK.

    • Claudia Langenberg
    • , Jing Hua Zhao
    • , Ruth J. F. Loos
    •  & Nicholas J. Wareham
  36. Department of Psychology, The University of Edinburgh, Edinburgh EH8 9JZ, UK.

    • Lorna M. Lopez
    •  & Ian J. Deary
  37. Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh EH8 9JZ, UK.

    • Lorna M. Lopez
    • , Sarah E. Harris
    • , John M. Starr
    • , Ian J. Deary
    •  & Peter M. Visscher
  38. Department of Clinical Chemistry, Fimlab Laboratories, Tampere University Hospital, FIN-33521 Tampere, Finland.

    • Leo-Pekka Lyytikäinen
    •  & Terho Lehtimäki
  39. Department of Clinical Chemistry, University of Tampere School of Medicine, FIN-33521 Tampere, Finland.

    • Leo-Pekka Lyytikäinen
    •  & Terho Lehtimäki
  40. Department of Clinical Sciences, Lund University, SE-205 02Malmö, Sweden.

    • Olle Melander
    • , Gunnar Engström
    • , Bo Hedblad
    •  & J. Gustav Smith
  41. Institute of Population Genetics, National Research Council of Italy, 07100 Sassari, Italy.

    • Federico Murgia
    • , Laura Portas
    •  & Mario Pirastu
  42. Department of Epidemiology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands.

    • Ilja M. Nolte
    •  & Harold Snieder
  43. Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, United Kingdom.

    • Sandosh Padmanabhan
    • , Claire E. Hastie
    •  & Anna F. Dominiczak
  44. University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.

    • Afshin Parsa
    • , Quince D. Gibson
    • , Braxton D. Mitchell
    •  & Alan R. Shuldiner
  45. Institute for Maternal and Child Health–IRCCS “Burlo Garofolo”–Trieste, University of Trieste, 34137 Trieste, Italy.

    • Nicola Pirastu
    • , Giorgia Girotto
    • , Antonietta Robino
    • , Adamo Pio d’Adamo
    •  & Paolo Gasparini
  46. Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, c/o Cittadella Universitaria di Monserrato, Monserrato, Cagliari 09042, Italy.

    • Eleonora Porcu
    • , Lucia Perseu
    • , Francesco Cucca
    • , Serena Sanna
    •  & Manuela Uda
  47. Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, D-85764 Neuherberg, Germany.

    • Janina S. Ried
    •  & Christian Gieger
  48. Queensland Institute of Medical Research, Brisbane, Queensland 4006, Australia.

    • Clara S. Tang
    • , Beben Benyamin
    • , Sarah E. Medland
    • , John B. Whitfield
    • , Nicholas G. Martin
    • , Grant W. Montgomery
    • , Peter M. Visscher
    •  & Manuel A. Ferreira
  49. Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, D-17487 Greifswald, Germany.

    • Alexander Teumer
    •  & Uwe Völker
  50. Division of Genetics and Cell Biology, San Raffaele Scientific Institute, 20132 Milano, Italy.

    • Michela Traglia
    • , Giorgio Pistis
    • , Cinzia Sala
    •  & Daniela Toniolo
  51. Institute for Maternal and Child Health - IRCCS “Burlo Garofolo”- Trieste, 34137 Trieste, Italy.

    • Sheila Ulivi
  52. University of Queensland Diamantina Institute, The University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland 4102, Australia.

    • Jian Yang
    •  & Peter M. Visscher
  53. Inserm, CESP Centre for research in Epidemiology and Population Health, U1018, Villejuif F-94807, France.

    • Beverley Balkau
  54. University Paris Sud 11, UMRS 1018, Villejuif F-94807, France.

    • Beverley Balkau
  55. Geriatric Unit, Azienda Sanitaria Firenze, 50125 Florence, Italy.

    • Stefania Bandinelli
  56. Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland.

    • François Bastardot
    •  & Peter Vollenweider
  57. Department of Internal Medicine, University of Lausanne, CH-1011 Lausanne, Switzerland.

    • François Bastardot
    •  & Peter Vollenweider
  58. Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia.

    • Beben Benyamin
    •  & Peter M. Visscher
  59. Division of Endocrinology and Diabetes, Department of Medicine, University Hospital, Ulm D-89075, Germany.

    • Bernhard O. Boehm
  60. The Hatter Cardiovascular Institute, University College London, London WC1E 6HX, UK.

    • Debashish Das
  61. Division of Genetics, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.

    • Paul I. W. de Bakker
  62. Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.

    • Paul I. W. de Bakker
  63. Nutrition and Dietetics, Harokopio University, Kallithea 17671, Athens, Greece.

    • Maria Dimitriou
    •  & George V. Dedoussis
  64. Institute of Epidemiology I and Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, D-85764 Neuherberg, Germany.

    • Angela Döring
  65. The Laboratory in Mjodd, 108 Reykjavik, Iceland.

    • Gudmundur Ingi Eyjolfsson
  66. Clinical Research Branch, National Institute on Aging, Baltimore, Maryland 21250, USA.

    • Luigi Ferrucci
    •  & Toshiko Tanaka
  67. Instituto de Saúde Coletiva, Federal University of Bahia, Salvador, Bahia 40110-040, Brazil.

    • Quince D. Gibson
  68. Medical Genetics Section, The University of Edinburgh, Edinburgh EH4 2XU, UK.

    • Sarah E. Harris
  69. Institute of Clinical Sciences, Obstetrics and Gynecology, University of Oulu FIN-90220 Oulu, Finland.

    • Anna-Liisa Hartikainen
  70. Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, D-85764 Neuherberg, Germany.

    • Thomas Illig
  71. Hannover Unified Biobank, Hannover Medical School, D-30625 Hannover, Germany.

    • Thomas Illig
  72. Department of Clinical Physiology, Tampere University Hospital, FIN-33521 Tampere, Finland.

    • Mika Kähönen
  73. Department of Clinical Physiology, University of Tampere School of Medicine, FIN-33521 Tampere, Finland.

    • Mika Kähönen
  74. Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands.

    • Ido P. Kema
    •  & L. Joost van Pelt
  75. Department of Epidemiology, Department of Biostatistics, Harvard School of Public Health, Cambridge, Massachusetts 02115, USA.

    • Liming Liang
  76. Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, D-85764 Neuherberg, Germany.

    • Christa Meisinger
  77. Department of Twin Research and Genetic Epidemiology, Kings College London, London SE1 7EH, UK.

    • Yasin Memari
  78. Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, D-17475 Greifswald, Germany.

    • Matthias Nauck
  79. Department of Clinical Biochemistry, Landspitali University Hospital, 101 Reykjavik, Iceland.

    • Isleifur Olafsson
  80. Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland.

    • Pall T. Onundarson
  81. Laboratory of Hematology and Coagulation Disorder Center, Landspitali University Hospital, 101 Reykjavik, Iceland.

    • Pall T. Onundarson
  82. Genetic Park of Ogliastra, Perdasdefogu, Sardinia, Italy.

    • Debora Parracciani
  83. Department of Psychiatry/EMGO Institute/Neuroscience Campus, VU University Medical Centre, 1081 BT Amsterdam, The Netherlands.

    • Brenda W. Penninx
    •  & Johannes H. Smit
  84. Department of Psychiatry, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands.

    • Brenda W. Penninx
  85. Department of Psychiatry, Leiden University Medical Centre, 2333 Leiden, The Netherlands.

    • Brenda W. Penninx
  86. Division of Pediatrics and Thalassemia Centre, Department of Clinical and Biological Sciences, University of Torino, 10043 Orbassano, Turin, Italy.

    • Antonio Piga
  87. Institute of Health Sciences, University of Oulu, FIN-90220 Oulu, Finland.

    • Anneli Pouta
    •  & Marjo-Riitta Jarvelin
  88. National Institute of Health and Welfare, Aapistie 1, P.O. Box 310, FIN-90101 Oulu, Finland.

    • Anneli Pouta
  89. Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, FIN-20521 Turku, Finland.

    • Olli Raitakari
  90. Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, FIN-20521 Turku, Finland.

    • Olli Raitakari
  91. The School of Social and Community Medicine, University of Bristol, Bristol BS8 2PS, UK.

    • Susan M. Ring
  92. Institute of Diagnostics, University of Oulu, FIN-90014 Oulu, Finland.

    • Aimo Ruokonen
  93. Competence Centre on Reproductive Medicine and Biology, 50410 Tartu, Estonia.

    • Andres Salumets
  94. Institute of General and Molecular Pathology, University of Tartu, 51014 Tartu, Estonia.

    • Andres Salumets
  95. Department of Experimental Hematology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands.

    • Hein Schepers
  96. Department of Stem Cell Biology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands.

    • Hein Schepers
  97. Institute for Community Medicine, University Medicine Greifswald, D-17475 Greifswald, Germany.

    • Carsten Oliver Schmidt
  98. Departments of Human Genetics and Medicine, Faculty of Medicine, McGill University, Montreal, Quebec H3A 1B1, Canada.

    • Rob Sladek
  99. Geriatric Medicine Unit, The University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK.

    • John M. Starr
  100. Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland.

    • Unnur Thorsteinsdottir
    •  & Kari Stefansson
  101. ClinPhenomics Study Center, D-60594 Frankfurt, Germany.

    • Bernhard R. Winkelmann
  102. Utrecht Stroke Center, Department of Neurology and Neurosurgery, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands.

    • Ale Algra
  103. Dipartimento di Scienze Biomediche, Università di Sassari, 07100 Sassari, Italy.

    • Francesco Cucca
  104. Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK.

    • John Danesh
    •  & Carmel Moore
  105. MRC-HPA Centre for Environment and Health, Imperial College London, London W2 1PG, UK.

    • Paul Elliott
    •  & Marjo-Riitta Jarvelin
  106. Department of Cancer Biology, Thomas Jefferson University Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA.

    • Paolo Fortina
  107. Dipartimento di Medicina Molecolare, Università La Sapienza, 00161 Roma, Italy.

    • Paolo Fortina
  108. Centre National de la Recherche Scientifique (CNRS)-Unité mixte de recherche (UMR) 8199, Lille Pasteur Institute, Lille 59100, France.

    • Philippe Froguel
  109. Department of Genomics of Common Disease, School of Public Health, Imperial College London, London W2 1PG, UK.

    • Philippe Froguel
  110. Institute for Immunology and Transfusion Medicine, University Medicine Greifswald, D-17487 Greifswald, Germany.

    • Andreas Greinacher
  111. Center for Cardiovascular Diagnostics and Prevention, Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.

    • Stanley L. Hazen
    •  & W. H. Wilson Tang
  112. Department of Lifecourse snd Service, National Institute for Health and Welfare, FIN-90101 Oulu, Finland.

    • Marjo-Riitta Jarvelin
  113. Biocenter Oulu, University of Oulu, FIN-90220 Oulu, Finland.

    • Marjo-Riitta Jarvelin
  114. Clinical Gerontology Unit, Box 251, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 2QQ, UK.

    • Kay Tee Khaw
  115. Synlab Academy, D-68165 Mannheim, Germany.

    • Winfried Maerz
  116. Department of Internal Medicine, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands.

    • Gerjan Navis
  117. Department of Neurology, General Central Hospital, 39100 Bolzano, Italy.

    • Peter P. Pramstaller
  118. Department of Neurology, University of Lübeck, D-23538 Lübeck, Germany.

    • Peter P. Pramstaller
  119. Institute for Genomics and Multiscale Biology, Mount Sinai School of Medicine, New York 10029-6574, USA.

    • Eric Schadt
  120. Geriatric Research and Education Clinical Center, Veterans Administration Medical Center, Baltimore, Maryland 21201, USA.

    • Alan R. Shuldiner
  121. Department of Cardiology, Lund University, 22185 Lund, Sweden.

    • J. Gustav Smith
  122. Department of Twin Research and Genetic Epidemiology, Kings College London, London SE1 7EH, UK.

    • Tim D. Spector
  123. Department of Medicine, University of Leipzig, Liebigstr. 18, D-04103 Leipzig, Germany.

    • Michael Stumvoll
    •  & Anke Tönjes
  124. University of Leipzig, IFB AdiposityDiseases, D-04103 Leipzig, Germany.

    • Michael Stumvoll
    •  & Anke Tönjes
  125. Insitute of Molecular Genetics, CNR, 27100 Pavia, Italy.

    • Daniela Toniolo
  126. Department of Endocrinology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands.

    • Bruce H. R. Wolffenbuttel
  127. Service of Medical Genetics, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland.

    • Jacques S. Beckmann
  128. Imperial College Healthcare NHS Trust, London W12 0HS, UK.

    • Jaspal S. Kooner
    •  & John C. Chambers

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Contributions

Study organisation: J.C.C., C.G., P.v.d.H., J.S.K., W.H.O. and N.S. Manuscript preparation: H.A., J.S.B., J.C.C., G.V.D., P.D., C.G., P.v.d.H., A.A.Hicks, J.S.K., I.M.-L., W.H.O., A.Radhakrishnan, A.Rendon, S.S., J.Sehmi, N.S., D.S.P., M.U., N.V. and W.Z. All authors reviewed and had the opportunity to comment on the manuscript. Data collection and analysis in the participating genome-wide association, replication and phenotype cohorts: ALSPAC: D.M.E., J.P.K., S.M.R., G.D.S; AMISH: Q.D.G., B.D.M., A.Parsa, A.R.S.; Beta-thalassaemia: F.A., F.D., P.Fortina, R.G, L.Perseu, A.Piga, S.S., M.U.; CBR: A.Attwood, J.D., S.F.G., H.L.-J., C.Moore, W.H.O., J.Sambrook; CoLAUS: F.B., J.S.B., M.H., P.V.; DeCODE: G.I.E., D.F.G., H.H., I.O., P.T.O., K.S., P.S., U.T.; DESIR: B.Balkau, C.D., P.Froguel, R.Sladek; EGCUT: T.E., K.F., A.M., E.M., A.S.; EPIC: K.-T.K., C.L., R.J.F.L., N.J.W., J.-H.Z.; Genebank: H.A., J.H., S.L.H., W.H.W.T.; INGI CARL: P.G., G.G., N.P.; INGI CILENTO: M.C., T.N., D.R., R.Sorice.; INGI FVG: A.P.d.A., A.Robino, S.U.; INGI Val Borbera: G.P., C.S., D.T., M.T.; KORA: A.D., C.G., T.I., C.Meisinger, J.S.R.; LBC: I.J.D., S.E.H., L.M.L., J.M.S.; LIFELINES: R.A.d.B., I.P.K., I.M.-L., G.N., P.v.d.H., L.J.v.P., N.V., B.H.R.W.; LOLIPOP: A.Al-Hussani, J.C.C., D.D., P.E., J.S.K., X.L., K.M., J.Scott, J.Sehmi, S.-T.T., W.Z.; LURIC: B.G., B.O.B., M.E.K., W.M., B.R.W.; MDC: A.F.D., G.E., B.H., C.E.H., O.M., S.P., J.G.S.; MICROS: M.G., A.AHicks, A.S.-P., P.P.P.; NESDA: I.M.N., B.W.P., J.H.S., H.Snieder; NFBC1966: A.-L.H., M.-R.J., P.F.O., A.Pouta, A.Ruokonen.; NTR: A.Abdellaoui, D.I.B., E.J.C.d.G., J.-J.H., M.H.d.M., G.Willemsen; OGP: F.M., D.P., L.Portas, M.P.; PREVEND: R.A.d.B., I.M.-L., G.N., P.v.d.H., W.H.v.G., D.J.v.V., N.V.; QIMR: B.Benyamin, M.A.F., N.G.M., S.E.M., G.W.M., C.S.T., P.M.V., J.B.W.; SardiNIA: F.C., E.P., S.S., M.U.; SHIP: A.G., M.Nauck, C.O.S., A.Teumer, U.V.; SMART: A.Algra, F.W.A., P.I.W.d.B., V.T.; SORBS: V.L., I.P., M.S., A.Tönjes.; TwinsUK: Y.M., S.-Y.S., N.S., T.D.S.; UKBS: J.J., W.H.O., N.S., J.Stephens; Young Finns: M.K., T.L., L.-P.L., O.R. Functional studies: Drosophila, U.E., F.S.D., A.A.Hicks, M.Novatchkova, J.M.P., U.P., C.X.W., G.Wirnsberger; expression profiling, W.O.C., L.Franke, L.L., M.F.M., A.Rendon, E.S., H.-J.W.; FAIRE, C.A.A., P.D., W.H.O., D.S.P., A.Rendon, N.S. Data analysis and bioinformatics: A.Al-Hussani, S.B., J.C.C., M.D., L.Ferrucci, P.v.d.H., S.K., X.L., I.M.-L., K.M., S.M., A.Radhakrishnan, A.Rendon, R.R.-S., H.Schepers, J.Sehmi, N.S., H.H.W.S., S.T., T.T., N.V., K.V., P.V., J.Y., W.Z.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Pim van der Harst or Christian Gieger or Jaspal S. Kooner or Willem H. Ouwehand or Nicole Soranzo or John C. Chambers.

Supplementary information

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  1. 1.

    Supplementary Information

    This file contains Supplementary Notes, Supplementary Tables 1-3 and 6-26 (see separate files for Supplementary Tables 4 and 5), Supplementary References and Supplementary Figures 1-8 – see contents list for details.

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  1. 1.

    Supplementary Tables

    This file contains Supplementary Table 4 (see Supplementary Information file for legend).

  2. 2.

    Supplementary Tables

    This file contains Supplementary Table 5 (see Supplementary Information file for legend).

About this article

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DOI

https://doi.org/10.1038/nature11677

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