Brief Communication abstract


Nature Genetics 41, 280 - 282 (2009)
Published online: 8 February 2009 | doi:10.1038/ng.307

New susceptibility locus for coronary artery disease on chromosome 3q22.3

Jeanette Erdmann1, Anika Gros zlighennig1,2, Peter S Braund3, Inke R König2, Christian Hengstenberg4, Alistair S Hall5, Patrick Linsel-Nitschke1, Sekar Kathiresan6, Ben Wright7, David-Alexandre Trégouët8, Francois Cambien8, Petra Bruse1, Zouhair Aherrahrou1, Arnika K Wagner1, Klaus Stark4, Stephen M Schwartz9, Veikko Salomaa10, Roberto Elosua11, Olle Melander12, Benjamin F Voight13, Christopher J O'Donnell14, Leena Peltonen15, David S Siscovick9, David Altshuler16, Piera Angelica Merlini17, Flora Peyvandi18, Luisa Bernardinelli19,20, Diego Ardissino21, Arne Schillert2, Stefan Blankenberg22, Tanja Zeller22, Philipp Wild22, Daniel F Schwarz2, Laurence Tiret8, Claire Perret8, Stefan Schreiber23, Nour Eddine El Mokhtari23, Arne Schäfer23, Winfried März24,25,26, Wilfried Renner25, Peter Bugert27, Harald Klüter27, Jürgen Schrezenmeir28, Diana Rubin28, Stephen G Ball5, Anthony J Balmforth5, H-Erich Wichmann29,30, Thomas Meitinger31,32, Marcus Fischer4, Christa Meisinger29, Jens Baumert29, Annette Peters29, Willem H Ouwehand33, Italian Atherosclerosis, Thrombosis, and Vascular Biology Working Group34, Myocardial Infarction Genetics Consortium34, Wellcome Trust Case Control Consortium34, Cardiogenics Consortium34, Panos Deloukas15, John R Thompson7, Andreas Ziegler2, Nilesh J Samani3 & Heribert Schunkert1

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We present a three-stage analysis of genome-wide SNP data in 1,222 German individuals with myocardial infarction and 1,298 controls, in silico replication in three additional genome-wide datasets of coronary artery disease (CAD) and subsequent replication in approx25,000 subjects. We identified one new CAD risk locus on 3q22.3 in MRAS (P = 7.44 times 10-13; OR = 1.15, 95% CI = 1.11–1.19), and suggestive association with a locus on 12q24.31 near HNF1A-C12orf43 (P = 4.81 times 10-7; OR = 1.08, 95% CI = 1.05–1.11).

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  1. Medizinische Klinik II, Universität zu Lübeck, 23538 Lübeck, Germany.
  2. Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck, 23538 Lübeck, Germany.
  3. Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, LE3 9QP, UK.
  4. Klinik und Poliklinik für Innere Medizin II, Universität Regensburg, 93053 Regensburg, Germany.
  5. LIGHT, University of Leeds, Leeds, LS1 3EX, UK.
  6. Cardiovascular Research Center and Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
  7. Departments of Health Sciences and Genetics, University of Leicester, LE1 7RH Leicester, UK.
  8. Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche UMR_S 525, Université Pierre et Marie Curie (UPMC) Univ. Paris 06, Paris, France.
  9. Cardiovascular Health Research Unit, Departments of Epidemiology and General Medicine, University of Washington, Seattle, Washington 98109, USA.
  10. Chronic Disease Epidemiology Unit, Department of Health Promotion and Chronic Disease Prevention, National Public Health Institute, FI-00271 Helsinki, Finland.
  11. Cardiovascular Epidemiology and Genetics Group, Institut Municipal d'Investigació Mèdica, Barcelona 08036; Ciber Epidemiología y Salud Pública (CIBERSP), Spain.
  12. Department of Clinical Sciences, Hypertension and Cardiovascular Diseases, University Hospital Malmö, Lund University, SE-20502 Malmö, Sweden.
  13. Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
  14. National Heart, Lung, and Blood Institute, National Institutes of Health, Framingham, Bethesda, Maryland 20824, USA.
  15. The Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
  16. Department of Molecular Biology and Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
  17. Division of Cardiology, Azienda Ospedaliera Niguarda Ca' Granda, 20162 Milan, Italy.
  18. Department of Internal Medicine and Medical Specialities, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Maggiore, Mangiagalli e Regina Elena, University of Milan, 20162 Milan, Italy.
  19. Department of Applied Health Sciences, University of Pavia, 27100 Italy.
  20. Biostatistics Unit, Medical Research Council, CB2 0SR Cambridge, UK.
  21. Division of Cardiology, Azienda Ospedaliero-Universitaria di Parma, 43100 Parma, Italy.
  22. Department of Medicine II, Johannes Gutenberg-University 55099 Mainz, Germany.
  23. Institut für Klinische Molekularbiologie, Christian-Albrechts Universität, 24118 Kiel, Germany.
  24. Synlab Centre of Laboratory Diagnostics Heidelberg, 69037 Heidelberg, Germany.
  25. Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, 8036 Graz, Austria.
  26. Department of Public Health, Social and Preventive Medicine, University of Heidelberg 69117 Heidelberg, Medical Faculty of Mannheim, 68131 Mannheim, Germany.
  27. Institute of Transfusion Medicine and Immunology, University of Heidelberg 69117 Heidelberg, Medical Faculty of Mannheim, 68131 Mannheim, Germany.
  28. Bundesforschungsanstalt für Ernährung und Lebensmittel, Institut für Physiologie und Biochemie der Ernährung, 24118 Kiel, Germany.
  29. Institute of Epidemiology, Helmholtz Zentrum München – German Research Center for Environmental Health, 85764 Neuherberg, Germany.
  30. Institute of Medical Information Science, Biometry and Epidemiology, LMU 80539 Munich, Germany.
  31. Institut für Humangenetik, Helmholtz Zentrum München, Deutsches Forschungszentrum für Umwelt und Gesundheit, 85764 Neuherberg, Germany.
  32. Institut für Humangenetik, Technische Universität München, 80333 München, Germany.
  33. Department of Haematology, University of Cambridge, Long Road, Cambridge, CB2 2PT, UK.
  34. A full list of members is provided in the Supplementary Note online.

Correspondence to: Jeanette Erdmann1 e-mail: j.erdmann@cardiogenics.eu