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

Nature Genetics volume 41, pages 280–282 (2009)Cite this article

Abstract

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 ∼25,000 subjects. We identified one new CAD risk locus on 3q22.3 in MRAS (P = 7.44 × 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 × 10−7; OR = 1.08, 95% CI = 1.05–1.11).

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Figure 1: Association results from Stage 1.

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Acknowledgements

We thank J. Stegmann, A. Medack, S. Wrobel and A. Thiemig for assistance. We thank M. Scholz and J. Neudert (Trium Analysis Online GmbH, Munich, Germany) for database management. The German Study was supported by the Deutsche Forschungsgemeinschaft and the German Federal Ministry of Education and Research (BMBF) in the context of the German National Genome Research Network (NGFN-2 and NGFN-plus). The WTCCC Study was funded by the Wellcome Trust. Recruitment of cases for the WTCCC Study was carried out by the British Heart Foundation (BHF) Family Heart Study Research Group and supported by the BHF and the UK Medical Research Council. We also acknowledge support of the Wellcome Trust Functional Genomics Initiative in Cardiovascular Genetics. The KORA research platform (KORA, Cooperative Research in the Region of Augsburg) was initiated and financed by the GSF-National Research centre for Environment and Health, which is funded by the German Federal Ministry of Education and Research and of the State of Bavaria. N.J.S. and S.G.B. are supported by Chairs funded by the BHF. Recruitment for the Italian Atherosclerosis, Thrombosis and Vascular Biology Working Group was supported by the “Associazione per lo Studio della Trombosi in Cardiologia.” The MIGen/IATVB genotyping was supported by a grant to D. Altshuler (R01HL087676) from the STAMPEED program of the National Heart, Lung, and Blood Institute, US National Institutes of Health. In addition, the MIGen study was supported by grants from the Fannie Rippel Foundation (to S.K.) and the Doris Duke Charitable Foundation (to S.K.). The Broad Institute Center for Genotyping and Analysis subsidized genotyping in the MIGen study with support from the National Center for Research Resources (U54RR020278). The main sponsor of the current analysis is the EU-funded integrated project Cardiogenics (LSHM-CT-2006-037593).

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Authors and Affiliations

  1. Medizinische Klinik II, Universität zu Lübeck, Lübeck, 23538, Germany

    Jeanette Erdmann, Anika Großhennig, Patrick Linsel-Nitschke, Petra Bruse, Zouhair Aherrahrou, Arnika K Wagner & Heribert Schunkert

  2. Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck, Lübeck, 23538, Germany

    Anika Großhennig, Inke R König, Arne Schillert, Daniel F Schwarz & Andreas Ziegler

  3. Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, LE3 9QP, UK

    Peter S Braund & Nilesh J Samani

  4. Klinik und Poliklinik für Innere Medizin II, Universität Regensburg, Regensburg, 93053, Germany

    Christian Hengstenberg, Klaus Stark & Marcus Fischer

  5. LIGHT, University of Leeds, Leeds, LS1 3EX, UK

    Alistair S Hall, Stephen G Ball & Anthony J Balmforth

  6. Cardiovascular Research Center and Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston, 02115, Massachusetts, USA

    Sekar Kathiresan

  7. Departments of Health Sciences and Genetics, University of Leicester, Leicester, LE1 7RH, UK

    Ben Wright & John R Thompson

  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

    David-Alexandre Trégouët, Francois Cambien, Laurence Tiret & Claire Perret

  9. Departments of Epidemiology and General Medicine, Cardiovascular Health Research Unit, University of Washington, Seattle, 98109, Washington, USA

    Stephen M Schwartz & David S Siscovick

  10. Department of Health Promotion and Chronic Disease Prevention, Chronic Disease Epidemiology Unit, National Public Health Institute, Helsinki, FI-00271, Finland

    Veikko Salomaa

  11. Cardiovascular Epidemiology and Genetics Group, Institut Municipal d'Investigació Mèdica, Barcelona 08036; Ciber Epidemiología y Salud Pública (CIBERSP), Spain

    Roberto Elosua

  12. Department of Clinical Sciences, Hypertension and Cardiovascular Diseases, University Hospital Malmö, Lund University, Malmö, SE-20502, Sweden

    Olle Melander

  13. Center for Human Genetic Research, Massachusetts General Hospital, Boston, 02114, Massachusetts, USA

    Benjamin F Voight

  14. National Heart, Lung, and Blood Institute, National Institutes of Health, Framingham, Bethesda, Maryland, 20824, USA

    Christopher J O'Donnell

  15. The Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, CB10 1SA, Cambridge, UK

    Leena Peltonen & Panos Deloukas

  16. Department of Molecular Biology and Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston, 02115, Massachusetts, USA

    David Altshuler

  17. Division of Cardiology, Azienda Ospedaliera Niguarda Ca' Granda, Milan, 20162, Italy

    Piera Angelica Merlini

  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, Milan, 20162, Italy

    Flora Peyvandi

  19. Department of Applied Health Sciences, University of Pavia, 27100, Italy

    Luisa Bernardinelli

  20. Biostatistics Unit, Medical Research Council, Cambridge, CB2 0SR, UK

    Luisa Bernardinelli

  21. Division of Cardiology, Azienda Ospedaliero-Universitaria di Parma, Parma, 43100, Italy

    Diego Ardissino

  22. Department of Medicine II, Johannes Gutenberg-University, Mainz, 55099, Germany

    Stefan Blankenberg, Tanja Zeller & Philipp Wild

  23. Institut für Klinische Molekularbiologie, Christian-Albrechts Universität, Kiel, 24118, Germany

    Stefan Schreiber, Nour Eddine El Mokhtari & Arne Schäfer

  24. Synlab Centre of Laboratory Diagnostics Heidelberg, Heidelberg, 69037, Germany

    Winfried März

  25. Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, 8036, Austria

    Winfried März & Wilfried Renner

  26. Department of Public Health, Social and Preventive Medicine, University of Heidelberg 69117 Heidelberg, Medical Faculty of Mannheim, Mannheim, 68131, Germany

    Winfried März

  27. Institute of Transfusion Medicine and Immunology, University of Heidelberg 69117 Heidelberg, Medical Faculty of Mannheim, Mannheim, 68131, Germany

    Peter Bugert & Harald Klüter

  28. Bundesforschungsanstalt für Ernährung und Lebensmittel, Institut für Physiologie und Biochemie der Ernährung, Kiel, 24118, Germany

    Jürgen Schrezenmeir & Diana Rubin

  29. Institute of Epidemiology, Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, 85764, Germany

    H-Erich Wichmann, Christa Meisinger, Jens Baumert & Annette Peters

  30. Institute of Medical Information Science, Biometry and Epidemiology, Munich, LMU 80539, Germany

    H-Erich Wichmann

  31. Institut für Humangenetik, Helmholtz Zentrum München, Deutsches Forschungszentrum für Umwelt und Gesundheit, Neuherberg, 85764, Germany

    Thomas Meitinger

  32. Institut für Humangenetik, Technische Universität München, München, 80333, Germany

    Thomas Meitinger

  33. Department of Haematology, University of Cambridge, Long Road, Cambridge, CB2 2PT, UK

    Willem H Ouwehand

Authors
  1. Jeanette Erdmann
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  2. Anika Großhennig
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  3. Peter S Braund
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  4. Inke R König
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  5. Christian Hengstenberg
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  6. Alistair S Hall
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  7. Patrick Linsel-Nitschke
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  8. Sekar Kathiresan
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  9. Ben Wright
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  10. David-Alexandre Trégouët
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  11. Francois Cambien
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  19. Olle Melander
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  20. Benjamin F Voight
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  22. Leena Peltonen
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Consortia

Italian Atherosclerosis, Thrombosis, and Vascular Biology Working Group

Myocardial Infarction Genetics Consortium

Wellcome Trust Case Control Consortium

Cardiogenics Consortium

Contributions

The study was designed by H.S., N.J.S., A.Z., I.R.K., J.R.T. and J.E. Subject ascertainment, recruitment and medical record review was organized and carried out by C.H., P.L.-N. and M.F. DNA material collection, handling and genotyping (Affymetrix 500K, 6.0, and TaqMan) was supervised by P.D., T.M., P. Bruse, W.H.O., P.S.B., K.S., C.P. and A. Schäfer Statistical analysis was carried out by A.G., D.F.S., I.R.K., B.W., A. Schillert, D.-A.T., J.R.T. and A.Z. RT-PCRs were carried out by Z.A. and A.K.W., J.E., N.J.S and H.S. drafted the manuscript with substantial contributions from I.R.K, A.G. and A.Z. Principal collaborators for the case cohorts were W.M. and W.R. (LURIC), H.K. and P. Bugert (GerBS), P.L.-N. (Angio-Luebeck), N.E.M., S.S., J.S. and D.R. (PopGen), H.-E.W., T.M., C.M., A.P., and J.B. (KORA), N.J.S., A.S.H., S.G.B., P.S.B. and A.J.B. (UKMI), C.H., M.F., K.S. (GO-KARD), S.K., D. Altshuler, B.F.V., D. Ardissino, O.M., C.J.O´D., R.E., V.S., L.P., D.S.S. and S.M.S. (MIGen), P.A.M., F.P., L.B. and D. Ardissino (IATVB), S.B., T.Z. and P.W. (Atherogene), L.T., C.P. and F.C. (ECTIM). All authors contributed to the final version of the manuscript.

Corresponding author

Correspondence to Jeanette Erdmann.

Additional information

A full list of members is provided in the Supplementary Note.

A full list of members is provided in the Supplementary Note.

A full list of members is provided in the Supplementary Note.

A full list of members is provided in the Supplementary Note.

Supplementary information

Supplementary Text and Figures

Supplementary Methods, Supplementary Figures 1–5, Supplementary Tables 1–4 and Supplementary Note (PDF 1382 kb)

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Erdmann, J., Großhennig, A., Braund, P. et al. New susceptibility locus for coronary artery disease on chromosome 3q22.3. Nat Genet 41, 280–282 (2009). https://doi.org/10.1038/ng.307

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