Article abstract


Nature Genetics 41, 1182 - 1190 (2009)
Published online: 11 October 2009 | doi:10.1038/ng.467

A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium

Nicole Soranzo1,2,45, Tim D Spector2,45, Massimo Mangino2,45, Brigitte Kühnel3, Augusto Rendon4, Alexander Teumer5, Christina Willenborg6,7, Benjamin Wright8, Li Chen9, Mingyao Li10, Perttu Salo11,12, Benjamin F Voight13,14, Philippa Burns4, Roman A Laskowski15, Yali Xue1, Stephan Menzel16, David Altshuler13,14,17,18,19, John R Bradley20, Suzannah Bumpstead1, Mary-Susan Burnett21, Joseph Devaney21, Angela Döring3, Roberto Elosua22, Stephen E Epstein21, Wendy Erber23, Mario Falchi2,24, Stephen F Garner4, Mohammed J R Ghori1, Alison H Goodall25, Rhian Gwilliam1, Hakon H Hakonarson26, Alistair S Hall27, Naomi Hammond1, Christian Hengstenberg28, Thomas Illig3, Inke R König6, Christopher W Knouff29, Ruth McPherson9, Olle Melander30, Vincent Mooser29, Matthias Nauck31, Markku S Nieminen32, Christopher J O'Donnell18,33, Leena Peltonen11,12, Simon C Potter1, Holger Prokisch34,35, Daniel J Rader36,37, Catherine M Rice1, Robert Roberts9, Veikko Salomaa11,12, Jennifer Sambrook4, Stefan Schreiber38, Heribert Schunkert7, Stephen M Schwartz39,40, Jovana Serbanovic-Canic4, Juha Sinisalo32, David S Siscovick39,40, Klaus Stark28, Ida Surakka12, Jonathan Stephens4, John R Thompson8, Uwe Völker5, Henry Völzke41, Nicholas A Watkins4, George A Wells9, H-Erich Wichmann3,42, David A Van Heel43, Chris Tyler-Smith1, Swee Lay Thein16, Sekar Kathiresan18,33, Markus Perola11,12, Muredach P Reilly36,37, Alexandre F R Stewart9, Jeanette Erdmann7, Nilesh J Samani25, Christa Meisinger3, Andreas Greinacher44, Panos Deloukas1,45, Willem H Ouwehand1,4,45 & Christian Gieger3,45


The number and volume of cells in the blood affect a wide range of disorders including cancer and cardiovascular, metabolic, infectious and immune conditions. We consider here the genetic variation in eight clinically relevant hematological parameters, including hemoglobin levels, red and white blood cell counts and platelet counts and volume. We describe common variants within 22 genetic loci reproducibly associated with these hematological parameters in 13,943 samples from six European population-based studies, including 6 associated with red blood cell parameters, 15 associated with platelet parameters and 1 associated with total white blood cell count. We further identified a long-range haplotype at 12q24 associated with coronary artery disease and myocardial infarction in 9,479 cases and 10,527 controls. We show that this haplotype demonstrates extensive disease pleiotropy, as it contains known risk loci for type 1 diabetes, hypertension and celiac disease and has been spread by a selective sweep specific to European and geographically nearby populations.

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  1. Human Genetics, Wellcome Trust Sanger Institute, Genome Campus, Hinxton, UK.
  2. Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
  3. Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
  4. Department of Haematology, University of Cambridge and National Health Service Blood and Transplant, Cambridge, UK.
  5. Interfaculty Institute for Genetics and Functional Genomics, Ernst-Moritz-Arndt-Universität Greifswald, Greifswald, Germany.
  6. Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck, Lübeck, Germany.
  7. Medizinische Klinik II, Universität zu Lübeck, Lübeck, Germany.
  8. Department of Health Sciences, University of Leicester, Leicester, UK.
  9. John & Jennifer Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
  10. Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  11. Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.
  12. The Institute of Molecular Medicine, University of Helsinki, Finland.
  13. Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.
  14. Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  15. European Bioinformatics Institute, Genome Campus, Hinxton, UK.
  16. Department of Haematology, King's College London, London, UK.
  17. Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, USA.
  18. Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
  19. Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
  20. Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, UK.
  21. Cardiovascular Research Institute, MedStar Research Institute, Washington Hospital Center, Washington, DC, USA.
  22. Cardiovascular Epidemiology and Genetics, Institut Municipal D'investigacio Medica and CIBER Epidemiología y Salud Pública, Barcelona, Spain.
  23. Haematology Department, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
  24. Section of Genomic Medicine, Imperial College London, South Kensington Campus, London, UK.
  25. Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, UK.
  26. The Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
  27. BHF Heart Research Centre, Clinical Cardiology, Leeds General Infirmary, Leeds, UK.
  28. Klinik und Poliklinik für Innere Medizin II, Universität Regensburg, Regensburg, Germany.
  29. Genetics Division, GlaxoSmithKline, King of Prussia, Pennsylvania, USA.
  30. Department of Clinical Sciences, Hypertension and Cardiovascular Diseases, University Hospital Malmö, Lund University, Malmö, Sweden.
  31. Institut für Klinische Chemie und Laboratoriumsmedizin, Ernst-Moritz-Arndt Universität Greifswald, Greifswald, Germany.
  32. Division of Cardiology, Department of Medicine, Helsinki University Central Hospital (HUCH), Helsinki, Finland.
  33. Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts, USA.
  34. Department of Human Genetics, Klinikum rechts der Isar, Technical University Munich, Munich, Germany.
  35. Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
  36. The Cardiovascular Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  37. The Institute for Translational Medicine and Therapeutics, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  38. Institut für Klinische Molekularbiologie, Christian-Albrechts Universität, Kiel, Germany.
  39. Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology, University of Washington, Seattle, Washington, USA.
  40. Department of Epidemiology, University of Washington, Seattle, Washington, USA.
  41. Institute for Community Medicine, Ernst-Moritz-Arndt-Universität Greifswald, Greifswald, Germany.
  42. Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität and Klinikum Grosshadern, Munich, Germany.
  43. Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
  44. Institut für Immunologie und Transfusionsmedizin, Ernst-Moritz-Arndt-Universität Greifswald, Greifswald, Germany.
  45. These authors contributed equally to this work.

Correspondence to: Nicole Soranzo1,2,45 e-mail: ns6@sanger.ac.uk



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