Article | Published:

New gene functions in megakaryopoiesis and platelet formation

Nature volume 480, pages 201208 (08 December 2011) | Download Citation

Abstract

Platelets are the second most abundant cell type in blood and are essential for maintaining haemostasis. Their count and volume are tightly controlled within narrow physiological ranges, but there is only limited understanding of the molecular processes controlling both traits. Here we carried out a high-powered meta-analysis of genome-wide association studies (GWAS) in up to 66,867 individuals of European ancestry, followed by extensive biological and functional assessment. We identified 68 genomic loci reliably associated with platelet count and volume mapping to established and putative novel regulators of megakaryopoiesis and platelet formation. These genes show megakaryocyte-specific gene expression patterns and extensive network connectivity. Using gene silencing in Danio rerio and Drosophila melanogaster, we identified 11 of the genes as novel regulators of blood cell formation. Taken together, our findings advance understanding of novel gene functions controlling fate-determining events during megakaryopoiesis and platelet formation, providing a new example of successful translation of GWAS to function.

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Acknowledgements

Reactome is supported by grants from the US National Institutes of Health (P41 HG003751), EU grant LSHG-CT-2005-518254 ‘ENFIN’, and the EBI Industry Programme. A.C. and D.L.S. are supported by the Wellcome Trust grants WT 082597/Z/07/Z and WT 077037/Z/05/Z and WT 077047/Z/05/Z, respectively. J.S.C. and K.V. are supported by the European Union NetSim training fellowship scheme (number 215820). A. Radhakrishnan, A.A., H.L.J., J.J., J.S. and W.H.O. are funded by the National Institute for Health Research, UK. Augusto Rendon is funded by programme grant RG/09/012/28096 from the British Heart Foundation. J.M.P. is supported by an Advanced ERC grant. IntAct is funded by the EC under SLING, grant agreement no. 226073 (Integrating Activity) within Research Infrastructures of the FP7, under PSIMEX, contract no. FP7-HEALTH-2007-223411. C.G. received support by the European Community’s Seventh Framework Programme (FP7/2007-2013), ENGAGE Consortium, grant agreement HEALTH-F4-2007- 201413. N.S. is supported by the Wellcome Trust (Grant Number 098051). Acknowledgements by individual participating studies are provided in Supplementary Information.

Author information

Author notes

    • Christian Gieger
    • , Aparna Radhakrishnan
    • , Ana Cvejic
    • , Weihong Tang
    • , Eleonora Porcu
    • , Giorgio Pistis
    • , Jovana Serbanovic-Canic
    • , Serena Sanna
    • , Andrew A. Hicks
    • , Augusto Rendon
    • , Manuel A. Ferreira
    • , Willem H. Ouwehand
    •  & Nicole Soranzo

    These authors contributed equally to this work.

Affiliations

  1. Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstr.1, 85764 Neuherberg, Germany.

    • Christian Gieger
    •  & Brigitte Kühnel
  2. Department of Haematology, University of Cambridge & NHS Blood and Transplant, Cambridge CB2 0PT, UK.

    • Aparna Radhakrishnan
    • , Ana Cvejic
    • , Jovana Serbanovic-Canic
    • , Stuart Meacham
    • , Katrin Voss
    • , Jonathan Stephens
    • , Antony Attwood
    • , Jennifer Jolley
    • , Heather Lloyd-Jones
    • , Jennifer Sambrook
    • , Augusto Rendon
    •  & Willem H. Ouwehand
  3. Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1HH/1SA, UK.

    • Aparna Radhakrishnan
    • , Ana Cvejic
    • , Jovana Serbanovic-Canic
    • , Stuart Meacham
    • , Ramiro Ramirez-Solis
    • , So-Youn Shin
    • , Stavroula Kanoni
    • , Antony Attwood
    • , Yasin Memari
    • , Tsun-Po Yang
    • , Panos Deloukas
    • , Derek Stemple
    • , Willem H. Ouwehand
    •  & Nicole Soranzo
  4. Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, Minnesota 55455-0354, USA.

    • Weihong Tang
    •  & Aaron R. Folsom
  5. Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, c/o Cittadella Universitaria di Monserrato, Monserrato, Cagliari 09042, Italy.

    • Eleonora Porcu
    • , Francesco Cucca
    • , Andrea Maschio
    • , Manuela Uda
    •  & Serena Sanna
  6. San Raffaele Scientific Institute<, Via Olgettina 58, 20132 Milano, Italy.

    • Giorgio Pistis
    • , Cinzia Sala
    •  & Daniela Toniolo
  7. IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, 1030 Vienna, Austria.

    • Ulrich Elling
    •  & Josef Penninger
  8. Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Groby Road, Leicester LE3 9QP, UK.

    • Alison H. Goodall
    •  & Nilesh J. Samani
  9. Leicester NIHR Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester LE3 9QP, UK.

    • Alison H. Goodall
    •  & Nilesh J. Samani
  10. CNRS-UMR-8199, Institut de Biologie de Lille, 1 Rue du Professor Calmette, BP245, 59019 Lille Cedex, France.

    • Yann Labrune
    • , Amélie Bonnefond
    •  & Philippe Froguel
  11. Centre for Cognitive Ageing and Cognitive Epidemiology, 7 George Square, The University of Edinburgh, Edinburgh EH8 9JZ, UK.

    • Lorna M. Lopez
    • , David J. Porteous
    • , John M. Starr
    • , Peter M. Visscher
    •  & Ian J. Deary
  12. Department of Psychology, The University of Edinburgh, 7 George Square, Edinburgh EH8 9JZ, UK.

    • Lorna M. Lopez
    • , Gail Davies
    •  & Ian J. Deary
  13. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.

    • Reedik Mägi
  14. Laboratory for Statistical Analysis, RIKEN Center for Genomic Medicine, Institute of Physical and Chemical Research, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.

    • Yukinori Okada
    • , Atsushi Takahashi
    •  & Naoyuki Kamatani
  15. Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8654, Japan.

    • Yukinori Okada
  16. Institute for Maternal and Child Health — IRCCS ‘Burlo Garofolo’ — via dell’Istria 65/1, 34137 Trieste, Italy.

    • Nicola Pirastu
    • , Pio D’Adamo
    • , Sheila Ulivi
    •  & Paolo Gasparini
  17. Institute of Genetics and Biophysics A. Buzzati-Traverso, CNR, Via P. Castellino 111, 8031 Naples, Italy.

    • Rossella Sorice
    • , Daniela Ruggiero
    •  & Marina Ciullo
  18. Interfaculty Institute for Genetics and Functional Genomics, Ernst-Moritz-Arndt-University Greifswald, 17487 Greifswald, Germany.

    • Alexander Teumer
    •  & Uwe Völker
  19. Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, St Mary’s Campus, London W2 1PG, UK.

    • Weihua Zhang
    • , John C. Chambers
    •  & Paul Elliott
  20. Department of Medicine, University of Washington, 1959 Northeast Pacific Street, Seattle, Washington 98195-0001, USA.

    • Joshua C. Bis
    •  & Kerri L. Wiggins
  21. Institute of Clinical Molecular Biology, Christian-Albrechts-University, 24105 Kiel, Germany.

    • David Ellinghaus
    • , Stefan Schreiber
    •  & Andre Franke
  22. Centre for Biomedicine, European Academy Bozen/Bolzano, Viale Druso 1, 39100 Bolzano, Italy.

    • Martin Gögele
    • , Peter P. Pramstaller
    •  & Andrew A. Hicks
  23. Department of Biological Psychology, VU University Amsterdam, De Boelelaan 1105, Van der Boechorststraat 1, 1081 BT, Amsterdam, The Netherlands.

    • Jouke-Jan Hottenga
    • , Eco J. C. de Geus
    • , Gonneke Willemsen
    •  & Dorret I. Boomsma
  24. MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke’s Hospital, Box 285, Cambridge CB2 0QQ, UK.

    • Claudia Langenberg
    • , Ruth J. F. Loos
    • , Jing Hua Zhao
    •  & Nicholas J. Wareham
  25. Interdisciplinary Centre for Clinical Research, University of Leipzig, Inselstr. 22, 04103 Leipzig, Germany.

    • Peter Kovacs
  26. Department of Epidemiology and Biostatistics, Imperial College London, London W2 1PG, UK.

    • Paul F. O’Reilly
    •  & Marjo-Riitta Jarvelin
  27. Department of Twin Research and Genetic Epidemiology, King’s College London, London SE1 7EH, UK.

    • So-Youn Shin
    • , Chris Hammond
    • , Massimo Mangino
    • , Yasin Memari
    •  & Timothy D. Spector
  28. Estonian Genome Center, University of Tartu, Tiigi 61b, 50410 Tartu, Estonia.

    • Reedik Mägi
    • , Tõnu Esko
    • , Janne Pullat
    •  & Andres Metspalu
  29. Estonian Biocenter, Riia 23b, 51010, Tartu, Estonia.

    • Tõnu Esko
    •  & Andres Metspalu
  30. Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.

    • Tõnu Esko
    •  & Andres Metspalu
  31. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90089-9075, USA.

    • Jaana Hartiala
    •  & Hooman Allayee
  32. Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90089-9075, USA.

    • Jaana Hartiala
    •  & Hooman Allayee
  33. Department of Nutrition-Dietetics, Harokopio University, Athens 17671, Greece.

    • Stavroula Kanoni
    •  & George V. Dedoussis
  34. Institute of Population Genetics, National Council of Research, 07100 Sassari, Italy.

    • Federico Murgia
    • , Ginevra Biino
    •  & Mario Pirastu
  35. University of Maryland School of Medicine, 655 West Baltimore Street, Baltimore, Maryland 21201-1559, USA.

    • Afshin Parsa
    • , Quince D. Gibson
    • , Braxton D. Mitchell
    •  & Alan R. Shuldiner
  36. Department of Cardiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.

    • Pim van der Harst
    • , Rudolf A. de Boer
    • , Irene Mateo Leach
    •  & Dirk J. van Veldhuisen
  37. Department of Experimental Immunohaematology, Sanquin Research, Plesmanlaan 125, 1066 CX Amsterdam, The Netherlands and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.

    • C. Ellen van der Schoot
  38. Inserm, CESP Centre for research in Epidemiology and Population Health, U1018 Villejuif, 94807 France.

    • Beverley Balkau
  39. University Paris Sud 11, UMRS 1018, Villejuif, 94807 France.

    • Beverley Balkau
  40. Service de Médecine Interne, CHUV, 1011 Lausanne, Switzerland.

    • François Bastardot
  41. Division of Biostatistics, School of Public Health, University of Minnesota, A460 Mayo Building, mmc 303, 420 Delaware St SE, Minneapolis, Minnesota 55455, USA.

    • Saonli Basu
    •  & Wei Feng
  42. Institute for Community Medicine, Ernst-Moritz-Arndt-University Greifswald, 17475 Greifswald, Germany.

    • Sebastian E. Baumeister
  43. Shardna Life Sciences, Loc. Piscinamanna 09010 Pula (CA), Italy.

    • Ginevra Biino
    •  & Mario Pirastu
  44. Institute of Molecular Genetics-CNR Via Abbiategrasso 207, 27100 Pavia, Italy.

    • Ginevra Biino
    •  & Daniela Toniolo
  45. Istituto di Zootecnica, Universita’ Cattolica del Sacro Cuore sede Piacenza, via Emilia Parmense 84, 29122 Piacenza, Italy.

    • Lorenzo Bomba
  46. INSERM UMRS 937, Pierre and Marie Curie University (UPMC, Paris 6) and Medical School, 91 Bd de l’Hôpital, 75013 Paris, France.

    • François Cambien
  47. Institute of Epidemiology I, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstr.1, 85764 Neuherberg, Germany.

    • Angela Döring
    •  & H.-Erich Wichmann
  48. Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstr.1, 85764 Neuherberg, Germany.

    • Angela Döring
    •  & Christa Meisinger
  49. MRC-HPA Centre for Environment and Health, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, UK.

    • Paul Elliott
  50. Universität zu Lübeck, Medizinische Klinik 2, Lübeck Germany.

    • Jeanette Erdmann
    •  & Heribert Schunkert
  51. MRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK.

    • David M. Evans
    •  & Susan M. Ring
  52. Department of Genomics of Common Disease, School of Public Health, Imperial College London, The Commonwealth Building, The Hammersmith Hospital, Du Care Road, London W12 ONN, UK.

    • Mario Falchi
    •  & Philippe Froguel
  53. The University of Queensland Diamantina Institute, Princess Alexandra Hospital, Brisbane, Queensland 4102, Australia.

    • Ian H. Frazer
  54. Department of Medicine, Boston University, Boston, Massachusetts 02118, USA.

    • Nicole L. Glazer
  55. Department of Clinical Sciences/Obstetrics and Gynecology, University of Oulu, Aapistie 7, Oulu, 90220 Finland.

    • Anna-Liisa Hartikainen
    •  & Anneli Pouta
  56. Department of Epidemiology, University of Washington, Seattle, Washington 98195-7236, USA.

    • Susan R. Heckbert
    •  & Nicholas L. Smith
  57. Group Health Research Institute, Group Health Cooperative, Seattle, Washington 98101-1448, USA.

    • Susan R. Heckbert
    • , Nicholas L. Smith
    •  & Bruce M. Psaty
  58. Klinik und Poliklinik für Innere Medizin II, Universitätsklinikum Regensburg, 93053 Regensburg, Germany.

    • Christian Hengstenberg
  59. Department of Medical Genetics, University of Lausanne, and Swiss Institute of Bioinformatics, Lausanne, Switzerland.

    • Micha Hersch
  60. Unit for Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstr.1, 85764 Neuherberg, Germany.

    • Thomas Illig
  61. Department of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge, Cambridge CB1 8RN, UK.

    • Kay-Tee Khaw
  62. Clinical Gerontology Unit, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 2QQ, UK.

    • Kay-Tee Khaw
  63. First Department of Propedeutic Internal Medicine and Hematology Department, National and Kapodistrian University of Athens Medical School, Laikon General Hospital, Athens 11727, Greece.

    • Marie-Christine Kyrtsonis
  64. Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LJ, UK.

    • Vasiliki Lagou
    •  & Inga Prokopenko
  65. Department of Biostatistics, University of Washington, Seattle, Washington 98195-7232, USA.

    • Thomas Lumley
    •  & Barbara McKnight
  66. Genetic Epidemiology, Queensland Institute of Medical Research, The Bancroft Centre, 300 Herston Road, Herston 4006, Queensland, Australia.

    • Grant W. Montgomery
    • , Peter M. Visscher
    • , Nicholas G. Martin
    •  & Manuel A. Ferreira
  67. Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.

    • Yusuke Nakamura
  68. Institute of Clinical Chemistry and Laboratory Medicine, Ernst-Moritz-Arndt-University Greifswald, 17475 Greifswald, Germany.

    • Matthias Nauck
  69. Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.

    • Gerjan Navis
  70. Section for Epidemiology, Institute for Experimental Medicine, Christian-Albrechts-University Kiel, 24105 Kiel, Germany.

    • Ute Nöthlings
  71. Popgen Biobank, University Clinic Schleswig-Holstein, 24105 Kiel, Germany.

    • Ute Nöthlings
  72. Unit of Genetic Epidemiology and Bioinformatics, Department of Epidemiology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.

    • Ilja M. Nolte
    •  & Harold Snieder
  73. Medical Genetics Section, University of Edinburgh, Molecular Medicine Centre, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK.

    • David J. Porteous
  74. National Institute for Health and Welfare, Aapistie 1, Oulu 90220, Finland.

    • Anneli Pouta
  75. Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA.

    • Jerome I. Rotter
    •  & Kent Taylor
  76. Institute of Diagnostics, Clinical Chemistry, University of Oulu, Box 5000Y, University of Oulu, Oulu 90014, Finland.

    • Aimo Ruokonen
  77. NIHR Cambridge Biomedical Research Centre, Cambridge CB2 0QQ, UK.

    • Jennifer Sambrook
    • , John R. Bradley
    •  & Willem H. Ouwehand
  78. Laboratory of Genetics, National Institute on Aging, Baltimore, Maryland 21224-6825, USA.

    • David Schlessinger
  79. Faculty of Medicine, National Heart and Lung Institute, Cardiovascular Science, Hammersmith Campus, Hammersmith Hospital, Imperial College London, London W12 0HS, UK.

    • James Scott
    •  & Jaspal S. Kooner
  80. Seattle Epidemiologic Research and Information Center of the Department of Veterans Affairs Office of Research and Development, Seattle, Washington 98108, USA.

    • Nicholas L. Smith
  81. Geriatric Medicine Unit, The University of Edinburgh, Royal Victoria, Craigleith Road, Edinburgh EH4 2DN, UK.

    • John M. Starr
  82. Department of Medicine, University of Leipzig, Liebigstr. 18, 04103 Leipzig, Germany.

    • Michael Stumvoll
    •  & Anke Tönjes
  83. Center for Cardiovascular Diagnostics and Prevention, Department of Cell Biology and Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio 44195, USA.

    • W. H. Wilson Tang
    •  & Stanley L. Hazen
  84. Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.

    • W. H. Wilson Tang
  85. Institute of Genetics and Molecular Medicine, MRC Human Genetics Unit, Edinburgh EH4 2XU, UK.

    • Albert Tenesa
  86. The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin Midlothian EH25 9RG, UK.

    • Albert Tenesa
  87. Department of Molecular Haematology, King’s College London, 125 Coldharbour Lane, London SE5 9NU, UK.

    • Swee Lay Thein
  88. Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität and Klinikum Grosshadern, Marchioninistr. 15, 81377 Munich, Germany.

    • H.-Erich Wichmann
  89. Department of Physiatrics, Lapland Central Hospital, Rovaniemi, 96101, Finland.

    • Paavo Zitting
  90. Geriatric Research and Education Clinical Center, Veterans Administration Medical Center, Baltimore, Maryland 21208, USA.

    • Alan R. Shuldiner
  91. Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, 9713 GZ, Groningen, The Netherlands.

    • L. Joost van Pelt
  92. Sanquin Research Leiden, Jon J. van Rood Center for Clinical Transfusion research, and the Department of Immuno-hematology and Blood Transfusion, Leiden University Medical Center, 2333 Leiden, The Netherlands.

    • Jaap-Jan Zwaginga
  93. Division of Cardiovascular Medicine, University of Michigan Health System, Ann Arbor, Michigan, USA.

    • Santhi K. Ganesh
  94. Institute of Health Sciences, University of Oulu, Aapistie 7, Oulu, 90220 Finland.

    • Marjo-Riitta Jarvelin
  95. National Institute for Health and Welfare, Biocenter Oulu, University of Oulu, Aapistie 7, Oulu, 90220 Finland.

    • Marjo-Riitta Jarvelin
  96. Department of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, Washington 98101-1448, USA.

    • Bruce M. Psaty
  97. Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, 3584 CX Utrecht, Netherlands.

    • Jan-Willem N. Akkerman
  98. Institute for Immunology and Transfusion Medicine, Ernst-Moritz-Arndt-University Greifswald, 17475 Greifswald, Germany.

    • Andreas Greinacher
  99. Proteomics Services, EMBL–European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK.

    • Steve Jupe
    •  & Jyoti Khadake
  100. MRC Biostatistics Unit, Institute of Public Health, University Forvie Site, Robinson Way, Cambridge CB2 0SR, UK.

    • Lorenz Wernisch
    •  & Augusto Rendon
  101. Nordic Center of Cardiovascular Research, Lubeck, Germany.

    • Jeanette Erdmann
    •  & Heribert Schunkert
  102. University of Trieste, Piazzale Europa 1, 34127 Trieste, Italy.

    • Nicola Pirastu
    • , Pio D’Adamo
    •  & Paolo Gasparini

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Contributions

Study design group: C.G., S. Sanna, A.A.H., A. Rendon, M.A.F., W.H.O., N.S.; manuscript writing group: C.G., A. Radhakrishnan, S. Sanna, A.A.H., A. Rendon, M.A.F., W.H.O., N.S.; data preparation, meta-analysis and secondary analysis group: A. Radhakrishnan, B.K., W.T., E.P., G.P., R.M., M.A.F., C.G., N.S.; bioinformatics analyses, pathway analyses and protein–protein interaction network group: S.M., J.-W.N.A., S.J., J.K., Y.M., L.B., A. Rendon, W.H.O.; transcript profiling methods and data group: K.V., A. Rendon, L.W., A.H.G., T.-P.Y., F. Cambien, J.E., C. Hengstenberg, N.J.S., H. Schunkert, P.D., W.H.O.; M. musculus models: R.R.-S.; D. rerio knockdown models: A.C., J.S.-C., D. Stemple, W.H.O.; D. melanogaster knockdown models: U.E., J. Penninger and A.A.H. All other author contributions and roles are listed in Supplementary Information.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Christian Gieger or Willem H. Ouwehand or Nicole Soranzo.

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    The file contains Supplementary Text, Supplementary References, Supplementary Acknowledgements and Author Contributions, Supplementary Tables 2-8 (see separate file for Supplementary Table 1), Supplementary Data and Supplementary Figures 1-6 - see the contents page for more details. This file was replaced online on 02 April 2012 as the Supplementary Tables and supplementary Figures were missing from the original file.

Excel files

  1. 1.

    Supplementary Table 1

    The table shows a summary of population descriptives, trait measurements and details of genotyping and analysis metrics and methods. This file was replaced on line on 13 April 2012 as the file originally posted on line erroneously contained Supplementary Tables 2-8.

Zip files

  1. 1.

    Supplementary Data

    The file shows Protein-protein interaction network, containing gene expression levels and other annotation features. This file was removed from our website on 13 April 2012 as the original file posted was corrupted. To download this information please go to the following link - https://haemgen.haem.cam.ac.uk/files/.

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/nature10659

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