Movatterモバイル変換

[0]ホーム
URL:

Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Advertisement

Nature Genetics
  • Article
  • Published:

Large-scale association analysis identifies new risk loci for coronary artery disease

Nature Geneticsvolume 45, pages25–33 (2013)Cite this article

Subjects

Abstract

Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r2 < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networks comprising 85% of these putative genes involved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CAD and identifies key biological pathways.

This is a preview of subscription content,access via your institution

Access options

Access through your institution

Subscription info for Japanese customers

We have a dedicated website for our Japanese customers. Please go tonatureasia.com to subscribe to this journal.

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

￥ 4,980

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Canonical pathway analysis.

Similar content being viewed by others

References

  1. Berry, J.D. et al. Lifetime risks of cardiovascular disease.N. Engl. J. Med.366, 321–329 (2012).

    Article CAS PubMed PubMed Central  Google Scholar 

  2. Peden, J.F. & Farrall, M. Thirty-five common variants for coronary artery disease: the fruits of much collaborative labour.Hum. Mol. Genet.20 R2, R198–R205 (2011).

    Article CAS PubMed PubMed Central  Google Scholar 

  3. Kingsmore, S.F., Lindquist, I.E., Mudge, J., Gessler, D.D. & Beavis, W.D. Genome-wide association studies: progress and potential for drug discovery and development.Nat. Rev. Drug Discov.7, 221–230 (2008).

    Article CAS PubMed PubMed Central  Google Scholar 

  4. Stein, E.A. et al. Effect of a monoclonal antibody to PCSK9 on LDL cholesterol.N. Engl. J. Med.366, 1108–1118 (2012).

    Article CAS PubMed  Google Scholar 

  5. Schunkert, H. et al. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease.Nat. Genet.43, 333–338 (2011).

    Article CAS PubMed PubMed Central  Google Scholar 

  6. Coronary Artery Disease (C4D) Genetics Consortium. A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease.Nat. Genet.43, 339–344 (2011).

  7. Clarke, R. et al. Genetic variants associated with Lp(a) lipoprotein level and coronary disease.N. Engl. J. Med.361, 2518–2528 (2009).

    Article CAS PubMed  Google Scholar 

  8. Samani, N.J. et al. Genomewide association analysis of coronary artery disease.N. Engl. J. Med.357, 443–453 (2007).

    Article CAS PubMed PubMed Central  Google Scholar 

  9. Erdmann, J. et al. New susceptibility locus for coronary artery disease on chromosome 3q22.3.Nat. Genet.41, 280–282 (2009).

    Article CAS PubMed PubMed Central  Google Scholar 

  10. Kathiresan, S. et al. Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants.Nat. Genet.41, 334–341 (2009).

    Article CAS PubMed  Google Scholar 

  11. Soranzo, N. et al. A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium.Nat. Genet.41, 1182–1190 (2009).

    Article CAS PubMed PubMed Central  Google Scholar 

  12. Wang, F. et al. Genome-wide association identifies a susceptibility locus for coronary artery disease in the Chinese Han population.Nat. Genet.43, 345–349 (2011).

    Article CAS PubMed  Google Scholar 

  13. The IBC 50K CAD Consortium. Large-scale gene-centric analysis identifies novel variants for coronary artery disease.PLoS Genet.7, e1002260 (2011).

  14. Yang, J. et al. Genome partitioning of genetic variation for complex traits using common SNPs.Nat. Genet.43, 519–525 (2011).

    Article CAS PubMed PubMed Central  Google Scholar 

  15. Voight, B.F. et al. The Metabochip, a custom genotyping array for genetic studies of metabolic, cardiovascular, and anthropometric traits.PLoS Genet.8, e1002793 (2012).

    CAS PubMed PubMed Central  Google Scholar 

  16. Teslovich, T.M. et al. Biological, clinical and population relevance of 95 loci for blood lipids.Nature466, 707–713 (2010).

    Article CAS PubMed PubMed Central  Google Scholar 

  17. International Consortium for Blood Pressure Genome-Wide Association Studies. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.Nature478, 103–109 (2011).

  18. Voight, B.F. et al. Twelve type 2 diabetes susceptibility loci identified through large scale association analysis.Nat. Genet.42, 579–589 (2010).

    Article CAS PubMed PubMed Central  Google Scholar 

  19. Dupuis, J. et al. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.Nat. Genet.42, 105–116 (2010).

    Article CAS PubMed PubMed Central  Google Scholar 

  20. Speliotes, E.K. et al. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index.Nat. Genet.42, 937–948 (2010).

    Article CAS PubMed PubMed Central  Google Scholar 

  21. Yang, J. et al. Conditional and joint multiple-SNP analysis of GWAS summary statistics identifies additional variants influencing complex traits.Nat. Genet.44, 369–375 (2012).

    Article CAS PubMed PubMed Central  Google Scholar 

  22. Ken-Dror, G., Talmud, P.J., Humphries, S.E. & Dreno, F.APOE/C1/C4/C2 gene cluster genotypes, haplotypes and lipid levels in prospective coronary heart disease risk among UK healthy men.Mol. Med.16, 389–399 (2010).

    Article CAS PubMed PubMed Central  Google Scholar 

  23. Reilly, M.P. et al. Identification ofADAMTS7 as a novel locus for coronary atherosclerosis and association ofABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies.Lancet377, 383–392 (2011).

    Article CAS PubMed PubMed Central  Google Scholar 

  24. Heid, I.M. et al. Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution.Nat. Genet.42, 949–960 (2010).

    Article CAS PubMed PubMed Central  Google Scholar 

  25. Storey, J.D. & Tibshirani, R. Statistical methods for identifying differentially expressed genes in DNA microarrays.Methods Mol. Biol.224, 149–157 (2003).

    CAS PubMed  Google Scholar 

  26. Hansson, G.K., Libby, P., Schönbeck, U. & Yan, Z.-Q. Innate and adaptive immunity in the pathogenesis of atherosclerosis.Circ. Res.91, 281–291 (2002).

    Article CAS PubMed  Google Scholar 

  27. Emerging Risk Factors Collaboration. Diabetes mellitus, fasting glucose, and risk of cause-specific death.N. Engl. J. Med.364, 829–841 (2011).

  28. Mozaffarian, D. et al. Incidence of new-onset diabetes and impaired fasting glucose in patients with recent myocardial infarction and the effect of clinical and lifestyle risk factors.Lancet370, 667–675 (2007).

    Article CAS PubMed  Google Scholar 

  29. Turnbull, F.M. et al. Intensive glucose control and macrovascular outcomes in type 2 diabetes.Diabetologia52, 2288–2298 (2009).

    Article CAS PubMed  Google Scholar 

  30. Ross, R. Atherosclerosis is an inflammatory disease.Am. Heart J.138, S419–S420 (1999).

    Article CAS PubMed  Google Scholar 

  31. Folkersen, L. et al. Association of genetic risk variants with expression of proximal genes identifies novel susceptibility genes for cardiovascular disease.Circ. Cardiovasc. Genet.3, 365–373 (2010).

    Article CAS PubMed  Google Scholar 

  32. Grundberg, E. et al. Mappingcis- andtrans-regulatory effects across multiple tissues in twins: the MuTHER Study.Nat. Genet.44, 1084–1089 (2012).

    Article CAS PubMed PubMed Central  Google Scholar 

  33. Schadt, E.E. et al. Mapping the genetic architecture of gene expression in human liver.PLoS Biol.6, e107 (2008).

    Article PubMed PubMed Central  Google Scholar 

  34. Ge, B. et al. Global patterns ofcis variation in human cells revealed by high-density allelic expression analysis.Nat. Genet.41, 1216–1222 (2009).

    Article CAS PubMed  Google Scholar 

Download references

Acknowledgements

We thank the personnel of the Wellcome Trust Sanger Institute (WTSI) Genotyping Facility, in particular S. Edkins, for supervising the genotyping of the AMC-PAS, Cardiogenics, GLACIER, MORGAM, PROMIS, THISEAS, and WTCCC cohorts.

AMC-PAS/SANQUIN.

We thank A.A. Soussan for technical assistance.

We thank personnel from the Estonian Genome Center of the University of Tartu (EGCUT) and the Estonian Biocentre, especially M. Hass and V. Soo, for data generation.

FINCAVAS.

We thank the staff of the Department of Clinical Physiology for collecting the exercise test data.

The GLACIER Study.

The GLACIER study is a nested study within the Northern Sweden Health and Disease Study; phenotyping was conducted as part of the Västerbotten Intervention Project. We thank the participants and the investigators from these studies for their valuable contributions, with specific thanks to L. Weinehall, Å. Agren, K. Enquist and T. Johansson.

GoDARTS Dundee.

We are grateful to all the participants who took part in this study, to the general practitioners, to the Scottish School of Primary Care for their help in recruiting the participants and to the whole team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. We acknowledge the support of the Health Informatics Centre at the University of Dundee in managing and supplying the anonymized data and National Health Service (NHS) Tayside, the original data owner.

Heart Protection Study.

The study was designed and conducted by the Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU) at the University of Oxford. Genotyping was supported by a grant to Oxford University and Centre National de Genotypage (CNG) from Merck. The funders had no role in the design of the study or in the data collection or analysis. We especially acknowledge the participants in the study, the Steering Committee and our collaborators. J.C.H. acknowledges support from the British Heart Foundation (BHF) Centre of Research Excellence.

LOLIPOP.

We thank the participants and research staff who made the study possible.

MORGAM study.

We thank the contributing sites and key personnel, as detailed below.

Finland: We thank FINRISK, National Institute for Health and Welfare, Helsinki: V.S. (principal investigator), A. Juolevi, E. Vartiainen and P. Jousilahti; Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) study, National Institute for Health and Welfare, Helsinki: J. Virtamo (principal investigator) and H. Kilpeläinen; the MORGAM Data Centre, National Institute for Health and Welfare, Helsinki: K. Kuulasmaa (responsible person), Z. Cepaitis, A. Haukijärvi, B. Joseph, J. Karvanen, S. Kulathinal, M. Niemelä and O. Saarela; and the MORGAM Central Laboratory, National Institute for Health and Welfare, Helsinki: M.P. (responsible person), P. Laiho and M. Sauramo.

France: We thank the National Coordinating Centre, National Institute of Health and Medical Research (U258), Paris: P. Ducimetière (national coordinator) and A. Bingham; Prospective Epidemiological Study of Myocardial Infarction (PRIME)/Strasbourg, Department of Epidemiology and Public Health, EA 3430, University of Strasbourg, Faculty of Medicine, Strasbourg: D. Arveiler (principal investigator), B. Haas and A. Wagner; PRIME/Toulouse, Department of Epidemiology, Toulouse University School of Medicine, Toulouse: J.F. (principal investigator), J.-B. Ruidavets, V. Bongard, D. Deckers, C. Saulet and S. Barrere; PRIME/Lille, Department of Epidemiology and Public Health, INSERM U744–Université Lille Nord de France–Institut Pasteur de Lille, Lille: P. Amouyel (principal investigator), M. Montaye, B. Lemaire, S. Beauchant, D. Cottel, C. Graux, N. Marecaux, C. Steclebout and S. Szeremeta; and the MORGAM Laboratory, INSERM U937, Paris: F.C. (responsible person), L. Tiret and V. Nicaud.

Italy: We thank Centro Ricerche EPIMED–Epidemiologia e Medicina Preventiva, Dipartimento di Medicina Clinica e Sperimentale; Università dell' Insubria, Varese: M.M.F. (principal investigator) and G. Veronesi; and Research Centre on Public Health, University of Milano–Bicocca, Monza: G. Cesana.

UK: We thank PRIME/Belfast, Queen's University Belfast, Belfast: F.K. (principal investigator), A.E. (former principal investigator), J. Yarnell and E. Gardner; and the MORGAM Coordinating Centre, Queen's University Belfast, Belfast: A.E. (MORGAM coordinator), S. Cashman and F.K.

MORGAM management group: A.E. (chair), S.S.B., F.C., M.M.F., K. Kuulasmaa, A. Palotie, M.P., A.P., V.S., H. Tunstall-Pedoe and P.G. Wiklund. Previous members: K. Asplund, L. Peltonen, D. Shields and B. Stegmayr. The PRIME Study is organized under an agreement between INSERM and the Merck, Sharpe and Dohme-Chibret Laboratory, with the following participating laboratories: The Strasbourg MONICA Project, Laboratoire d'Epidémiologie et de Santé Publique, and the Université de Strasbourg, Strasbourg, France (D. Arveiler and B. Haas); The Toulouse MONICA Project, UMR INSERM 1027, and the Department of Epidemiology, Toulouse University School of Medicine, Université Paul Sabatier, Toulouse, France (J.F. and J.-B. Ruidavets); The Lille MONICA Project, INSERM U744, Institut Pasteur de Lille and Université Lille Nord de France, Lille, France (P. Amouyel and M. Montaye); The Department of Epidemiology and Public Health, Queen's University, Belfast, Belfast, UK (A.E., J. Yarnell and F.K.); The Department of Atherosclerosis, INSERM U545, Institut Pasteur de Lille, Faculté de Médecine and Université Lille Nord de France, Lille, France (G. Luc and J.-M. Bard); The Laboratory of Haematology, INSERM U626, and Hôpital La Timone, Marseille, France (I. Juhan-Vague and P. Morange); The Laboratory of Endocrinology, INSERM U563, Toulouse, France (B. Perret); The Vitamin Research Unit, The University of Bern, Bern, Switzerland (F. Gey); The Nutrition and Metabolism Group, Centre for Public Health, Queen's University Belfast, Belfast, UK (J. Woodside and I. Young); The DNA Bank, INSERM/Université Pierre et Marie Curie (UPMC), Paris Université Unite Mixte de Recherche (UMRS) 937, Paris (F.C.); The Coordinating Centre, Institut Fédératif de Recherche Santé Publique (IFR 69), Villejuif, France (P. Ducimetière); and INSERM U970, Villejuif, France, and University Paris V, Paris Cardiovascular Research Centre (PAARC), Paris (A. Bingham).

PIVUS/Swedish Twin Registry.

We thank the SNP&SEQ Technology Platform in Uppsala (see URLs) for genotyping, in particular T. Axelsson, A.-C. Wiman and C. Pöntinen for excellent assistance.

Ulm (EMIL).

We thank the Centre of Excellence Baden-Wuerttemberg Metabolic Disorders.

WTCCC.

We thank the BHF Family Heart Study Research Group for the collection of the cases.

Author information

Author notes

  1. Panos Deloukas, Stavroula Kanoni, Christina Willenborg, Martin Farrall, Themistocles L Assimes, John R Thompson, Erik Ingelsson, Danish Saleheen, Jeanette Erdmann, Muredach P Reilly, Rory Collins, Sekar Kathiresan, Anders Hamsten, Jaspal S Kooner, Unnur Thorsteinsdottir, John Danesh, Colin N A Palmer, Robert Roberts, Hugh Watkins, Heribert Schunkert and Nilesh J Samani: These authors contributed equally to this work.

Authors and Affiliations

  1. Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.,

    Panos Deloukas, Stavroula Kanoni, Kathleen Stirrups, Inês Barroso, Sarah E Hunt, Cordelia Langford, Tsun-Po Yang, Willem H Ouwehand, Manjinder S Sandhu & Samuli Ripatti

  2. Institut für Integrative und Experimentelle Genomik, Universität zu Lübeck, Lübeck, Germany

    Christina Willenborg & Jeanette Erdmann

  3. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK

    Martin Farrall, Anuj Goel, Mark I McCarthy, John F Peden, N William Rayner, Dominique Gauguier & Hugh Watkins

  4. Radcliffe Department of Medicine, Cardiovascular Medicine, University of Oxford, Oxford, UK

    Martin Farrall, Jean-Baptiste Cazier, Anuj Goel & Hugh Watkins

  5. Department of Medicine, Stanford University School of Medicine, Stanford, California, USA

    Themistocles L Assimes, Benjamin A Goldstein, Joshua W Knowles & Thomas Quertermous

  6. Department of Health Sciences, University of Leicester, Leicester, UK

    John R Thompson

  7. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

    Erik Ingelsson, Stefan Gustafsson, Ci Song & Nancy L Pedersen

  8. Center for Non-Communicable Diseases, Karachi, Pakistan

    Danish Saleheen

  9. Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK

    Danish Saleheen, Asif Rasheed & John Danesh

  10. Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Danish Saleheen & Weang K Ho

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

    Inke R König & Andreas Ziegler

  12. Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden

    Åsa Johansson, Niclas Eriksson, Lars Wallentin & Agneta Siegbahn

  13. Division of Cardiovascular and Neuronal Remodelling, Multidisciplinary Cardiovascular Research Centre, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, UK

    Alistair S Hall

  14. Center for Genome Science, Korea National Institute of Health, Korea Center for Disease Control and Prevention, Yeonje-ri, Chungwon-gun, Korea

    Jong-Young Lee, Bok-Ghee Han & Ji-Young Lee

  15. Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA

    Cristen J Willer

  16. Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA

    Cristen J Willer

  17. Department of Epidemiology and Biostatistics, Imperial College London, London, UK

    John C Chambers & Weihua Zhang

  18. Estonian Genome Center, University of Tartu, Tartu, Estonia

    Tõnu Esko, Krista Fischer & Andres Metspalu

  19. Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia

    Tõnu Esko, Evelin Mihailov & Andres Metspalu

  20. Department of Medicine, Atherosclerosis Research Unit, Karolinska Institutet, Stockholm, Sweden

    Lasse Folkersen, Rona J Strawbridge, Per Eriksson & Anders Hamsten

  21. Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden

    Lasse Folkersen, Rona J Strawbridge, Per Eriksson & Anders Hamsten

  22. Department of Twin Research and Genetic Epidemiology, King's College London, London, UK

    Elin Grundberg

  23. Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland

    Aki S Havulinna, Kati Kristiansson, Kari Kuulasmaa, Veikko Salomaa, Jarmo Virtamo & Markus Perola

  24. Clinical Trial Service Unit, University of Oxford, Oxford, UK

    Jemma C Hopewell, Sarah Parish, Robert Clarke & Rory Collins

  25. Epidemiological Studies Unit, University of Oxford, Oxford, UK

    Jemma C Hopewell, Sarah Parish, Robert Clarke & Rory Collins

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

    Marcus E Kleber & Winfried März

  27. Ludwigshafen Risk and Cardiovascular Health (LURIC) Study, Freiburg, Germany

    Marcus E Kleber

  28. Department of Medical Sciences, Uppsala University, Uppsala, Sweden

    Per Lundmark, Anders Lundmark, Lars Lind & Ann-Christine Syvänen

  29. Department of Clinical Chemistry, Fimlab Laboratories, Tampere University Hospital, Tampere, Finland

    Leo-Pekka Lyytikäinen & Terho Lehtimäki

  30. Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere, Finland

    Leo-Pekka Lyytikäinen & Terho Lehtimäki

  31. Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, UK

    Suzanne Rafelt, Peter S Braund, Alison H Goodall & Nilesh J Samani

  32. Department of Clinical Sciences, Genetic & Molecular Epidemiology Unit, Lund University Diabetes Center, Skåne University Hospital, Malmö, Sweden

    Dmitry Shungin & Paul W Franks

  33. Department of Public Health & Clinical Medicine, Genetic Epidemiology & Clinical Research Group, Section for Medicine, Umeå University, Umeå, Sweden

    Dmitry Shungin & Paul W Franks

  34. Department of Odontology, Umeå University, Umeå, Sweden

    Dmitry Shungin & Paul W Franks

  35. deCODE Genetics, Reykjavik, Iceland

    Gudmar Thorleifsson, Hilma Holm, Kari Stefansson & Unnur Thorsteinsdottir

  36. Institute for Molecular Medicine FIMM, University of Helsinki, Helsinki, Finland

    Emmi Tikkanen & Peter J Wagner

  37. Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland

    Emmi Tikkanen, Peter J Wagner & Samuli Ripatti

  38. Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK

    Natalie Van Zuydam, Alex S F Doney, Andrew D Morris & Colin N A Palmer

  39. Department of Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Benjamin F Voight

  40. HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, USA

    Lindsay L Waite & Devin Absher

  41. Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA

    David Altshuler, Ron Do, Pierre Fontanillas & Sekar Kathiresan

  42. Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, USA

    David Altshuler

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

    David Altshuler & Ron Do

  44. Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA

    David Altshuler

  45. Division of Cardiovascular and Diabetes Research, Multidisciplinary Cardiovascular Research Centre, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, UK.,

    Anthony J Balmforth

  46. University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK

    Inês Barroso

  47. National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK

    Peter S Braund, Alison H Goodall & Nilesh J Samani

  48. Deutsches Herzzentrum München, Technische Universität München, Munich, Germany

    Christof Burgdorf, Thorsten Kessler, Moritz P Rumpf & Heribert Schunkert

  49. Practice of Gynecology, Ulm University Medical Centre, Ulm, Germany

    Simone Claudi-Boehm

  50. Biotherapeutics and Bioinnovation Center, Pfizer, South San Francisco, California, USA

    David Cox

  51. Department of Dietetics–Nutrition, Harokopio University, Athens, Greece

    Maria Dimitriou & George Dedoussis

  52. Klinik für Innere Medizin, Kreiskrankenhaus Rendsburg, Rendsburg, Germany

    NourEddine El Mokhtari & Diana Rubin

  53. Department of Molecular Medicine and Surgery, Cardiothoracic Surgery Unit, Karolinska Institutet, Stockholm, Sweden

    Anders Franco-Cereceda

  54. Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden

    Bruna Gigante, Karin Leander & Ulf de Faire

  55. Department of Clinical Sciences, Diabetes and Endocrinology, Lund University, University Hospital Malmö, Malmö, Sweden

    Leif Groop & Olle Melander

  56. Commissariat à l′Energie Atomique (CEA)–Genomics Institute, National Genotyping Centre, Paris, France

    Jörg Hager

  57. Department of Public Health & Clinical Medicine, Section for Nutritional Research, Umeå University, Umeå, Sweden

    Göran Hallmans

  58. Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA

    Hyun M Kang & Michael Boehnke

  59. Hannover Unified Biobank, Hannover Medical School, Hannover, Germany

    Thomas Illig & Norman Klopp

  60. First Cardiology Department, Onassis Cardiac Surgery Center 356, Athens, Greece

    Genovefa Kolovou

  61. Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland

    Johanna Kuusisto & Markku Laakso

  62. Medical Research Council (MRC) Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK

    Claudia Langenberg, Nicholas Wareham & Manjinder S Sandhu

  63. Transplantation Laboratory, Haartman Institute, University of Helsinki, Helsinki, Finland

    Marja-Liisa Lokki

  64. Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK

    Mark I McCarthy

  65. Oxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford, UK

    Mark I McCarthy

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

    Christa Meisinger & Annette Peters

  67. Institut National de la Santé et la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR) S937, Institute for Cardiometabolism and Nutrition (ICAN), Pierre and Marie Curie (Paris 6) University, Paris, France

    Seraya Maouche, Francois Cambien & David-Alexandre Trégouët

  68. Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-Universität, Munich, Germany

    Martina Müller-Nurasyid

  69. Chair of Epidemiology, Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany

    Martina Müller-Nurasyid

  70. Chair of Genetic Epidemiology, Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany

    Martina Müller-Nurasyid

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

    Martina Müller-Nurasyid

  72. Department of Cardiology, Heart Centre, Tampere University Hospital, Tampere, Finland

    Kjell Nikus

  73. Division of Endocrinology and Diabetes, Department of Internal Medicine, Ulm University Medical Centre, Ulm, Germany

    Silke Rosinger & Bernhard O Boehm

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

    Arne Schäfer & Stefan Schreiber

  75. Division of Epidemiology, Multidisciplinary Cardiovascular Research Centre (MCRC) University of Leeds, Leeds, UK

    Mohan Sivananthan

  76. Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, UK

    Mohan Sivananthan

  77. University of Ottawa Heart Institute, Cardiovascular Research Methods Centre Ontario, Ottawa, Ontario, Canada

    Alexandre F R Stewart, George A Wells & Robert Roberts

  78. Ruddy Canadian Cardiovascular Genetics Centre, Ottawa, Ontario, Canada

    Alexandre F R Stewart, George A Wells & Robert Roberts

  79. National Heart and Lung Institute (NHLI), Imperial College London, Hammersmith Hospital, London, UK

    Sian-Tsung Tan & Jaspal S Kooner

  80. Faculty of Medicine, University of Iceland, Reykjavik, Iceland

    Gudmundur Thorgeirsson, Villi Gudnason, Kari Stefansson & Unnur Thorsteinsdottir

  81. Department of Medicine, Landspitali University Hospital, Reykjavik, Iceland

    Gudmundur Thorgeirsson

  82. Department of Experimental Immunohematology, Sanquin, Amsterdam, The Netherlands

    C Ellen van der Schoot

  83. Center for Thrombosis and Hemostasis, University Medical Center Mainz, Johannes Gutenberg University Mainz, Mainz, Germany

    Philipp S Wild

  84. Department of Medicine 2, University Medical Center Mainz, Johannes Gutenberg University Mainz, Mainz, Germany

    Philipp S Wild

  85. Institut Pasteur de Lille, INSERM U744, Université Lille Nord de France, Lille, France

    Philippe Amouyel

  86. Department of Epidemiology and Public Health, EA3430, University of Strasbourg, Strasbourg, France

    Dominique Arveiler

  87. Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands

    Hanneke Basart & G Kees Hovingh

  88. Human Genetics Center, University of Texas Health Science Center, Houston, Texas, USA

    Eric Boerwinkle

  89. Department of Experimental Medicine, University of Milano–Bicocca, Monza, Italy

    Paolo Brambilla

  90. Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA

    Adrienne L Cupples

  91. National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA

    Adrienne L Cupples

  92. Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands

    Abbas Dehghan & Christopher O'Donnell

  93. Clinic for General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany

    Patrick Diemert & Stefan S Blankenberg

  94. Cardiovascular Research Institute, Washington Hospital Center, Washington, DC, USA

    Stephen E Epstein

  95. Centre for Public Health, The Queen's University of Belfast, Belfast, UK

    Alun Evans

  96. Department of Clinical and Experimental Medicine, Research Centre for Epidemiology and Preventive Medicine (EPIMED), University of Insubria, Varese, Italy

    Marco M Ferrario

  97. Department of Cardiology, Toulouse University School of Medicine, Rangueil Hospital, Toulouse, France

    Jean Ferrières

  98. INSERM UMR S872, Cordeliers Research Centre, Paris, France

    Dominique Gauguier

  99. Division of Research, Kaiser Permanente Northern California, Oakland, California, USA

    Alan S Go & Carlos Iribarren

  100. Icelandic Heart Association, Kopavogur, Iceland

    Villi Gudnason

  101. Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA

    Stanley L Hazen

  102. Cardiology Division, Department of Internal Medicine, Cardiovascular Genome Center, Yonsei University, Seoul, Korea

    Yangsoo Jang

  103. Department of Clinical Physiology, Tampere University Hospital and University of Tampere, Tampere, Finland

    Mika Kähönen

  104. UK Clinical Research Collaboration (UKCRC) Centre of Excellence for Public Health (Northern Ireland), Queen's University of Belfast, Belfast, UK

    Frank Kee

  105. Department of Internal Medicine, Cardiovascular Center, Seoul National University Hospital, Seoul, Korea

    Hyo-Soo Kim

  106. Department of Internal Medicine II–Cardiology, Ulm University Medical Center, Ulm, Germany

    Wolfgang Koenig

  107. Science Center, Tampere University Hospital,

    Wolfgang Kratzer & Reijo Laaksonen

  108. Tampere, Finland

    Wolfgang Kratzer & Reijo Laaksonen

  109. Department of Haematology, University of Cambridge, Cambridge, UK

    Willem H Ouwehand

  110. National Health Service (NHS) Blood and Transplant, Cambridge, UK

    Willem H Ouwehand

  111. Division of Cardiology, Samsung Medical Center, Seoul, Korea

    Jeong E Park

  112. Munich Heart Alliance, Munich, Germany

    Annette Peters

  113. Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Daniel J Rader

  114. Department of Genetics and Genomic Sciences, Institute for Genomics and Multiscale Biology, Mount Sinai School of Medicine, New York, New York, USA

    Eric Schadt

  115. Department of Medicine, Center for Human Genetics, Duke University Medical Center, Durham, North Carolina, USA

    Svati H Shah

  116. Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA

    Svati H Shah

  117. Division of Cardiology, Department of Medicine, Helsinki University Central Hospital (HUCH), Helsinki, Finland

    Juha Sinisalo & Markku S Nieminen

  118. Klinik und Poliklinik für Innere Medizin II, Regensburg, Germany

    Klaus Stark, Martina E Zimmermann & Christian Hengstenberg

  119. Department of Human Genetics, McGill University, Montréal, Québec, Canada

    Tomi Pastinen

  120. Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA

    Paul W Franks

  121. Lebanese American University, Chouran, Beirut, Lebanon

    Pierre A Zalloua

  122. Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Muredach P Reilly

  123. Synlab Academy, Mannheim, Germany

    Winfried März

  124. Cardiology Division, Center for Human Genetic Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA

    Sekar Kathiresan

  125. Cardiovascular Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA

    Sekar Kathiresan

Authors
  1. Panos Deloukas
  2. Stavroula Kanoni
  3. Christina Willenborg
  4. Martin Farrall
  5. Themistocles L Assimes
  6. John R Thompson
  7. Erik Ingelsson
  8. Danish Saleheen
  9. Jeanette Erdmann
  10. Benjamin A Goldstein
  11. Kathleen Stirrups
  12. Inke R König
  13. Jean-Baptiste Cazier
  14. Åsa Johansson
  15. Alistair S Hall
  16. Jong-Young Lee
  17. Cristen J Willer
  18. John C Chambers
  19. Tõnu Esko
  20. Lasse Folkersen
  21. Anuj Goel
  22. Elin Grundberg
  23. Aki S Havulinna
  24. Weang K Ho
  25. Jemma C Hopewell
  26. Niclas Eriksson
  27. Marcus E Kleber
  28. Kati Kristiansson
  29. Per Lundmark
  30. Leo-Pekka Lyytikäinen
  31. Suzanne Rafelt
  32. Dmitry Shungin
  33. Rona J Strawbridge
  34. Gudmar Thorleifsson
  35. Emmi Tikkanen
  36. Natalie Van Zuydam
  37. Benjamin F Voight
  38. Lindsay L Waite
  39. Weihua Zhang
  40. Andreas Ziegler
  41. Devin Absher
  42. David Altshuler
  43. Anthony J Balmforth
  44. Inês Barroso
  45. Peter S Braund
  46. Christof Burgdorf
  47. Simone Claudi-Boehm
  48. David Cox
  49. Maria Dimitriou
  50. Ron Do
  51. Alex S F Doney
  52. NourEddine El Mokhtari
  53. Per Eriksson
  54. Krista Fischer
  55. Pierre Fontanillas
  56. Anders Franco-Cereceda
  57. Bruna Gigante
  58. Leif Groop
  59. Stefan Gustafsson
  60. Jörg Hager
  61. Göran Hallmans
  62. Bok-Ghee Han
  63. Sarah E Hunt
  64. Hyun M Kang
  65. Thomas Illig
  66. Thorsten Kessler
  67. Joshua W Knowles
  68. Genovefa Kolovou
  69. Johanna Kuusisto
  70. Claudia Langenberg
  71. Cordelia Langford
  72. Karin Leander
  73. Marja-Liisa Lokki
  74. Anders Lundmark
  75. Mark I McCarthy
  76. Christa Meisinger
  77. Olle Melander
  78. Evelin Mihailov
  79. Seraya Maouche
  80. Andrew D Morris
  81. Martina Müller-Nurasyid
  82. Kjell Nikus
  83. John F Peden
  84. N William Rayner
  85. Asif Rasheed
  86. Silke Rosinger
  87. Diana Rubin
  88. Moritz P Rumpf
  89. Arne Schäfer
  90. Mohan Sivananthan
  91. Ci Song
  92. Alexandre F R Stewart
  93. Sian-Tsung Tan
  94. Gudmundur Thorgeirsson
  95. C Ellen van der Schoot
  96. Peter J Wagner
  97. George A Wells
  98. Philipp S Wild
  99. Tsun-Po Yang
  100. Philippe Amouyel
  101. Dominique Arveiler
  102. Hanneke Basart
  103. Michael Boehnke
  104. Eric Boerwinkle
  105. Paolo Brambilla
  106. Francois Cambien
  107. Adrienne L Cupples
  108. Ulf de Faire
  109. Abbas Dehghan
  110. Patrick Diemert
  111. Stephen E Epstein
  112. Alun Evans
  113. Marco M Ferrario
  114. Jean Ferrières
  115. Dominique Gauguier
  116. Alan S Go
  117. Alison H Goodall
  118. Villi Gudnason
  119. Stanley L Hazen
  120. Hilma Holm
  121. Carlos Iribarren
  122. Yangsoo Jang
  123. Mika Kähönen
  124. Frank Kee
  125. Hyo-Soo Kim
  126. Norman Klopp
  127. Wolfgang Koenig
  128. Wolfgang Kratzer
  129. Kari Kuulasmaa
  130. Markku Laakso
  131. Reijo Laaksonen
  132. Ji-Young Lee
  133. Lars Lind
  134. Willem H Ouwehand
  135. Sarah Parish
  136. Jeong E Park
  137. Nancy L Pedersen
  138. Annette Peters
  139. Thomas Quertermous
  140. Daniel J Rader
  141. Veikko Salomaa
  142. Eric Schadt
  143. Svati H Shah
  144. Juha Sinisalo
  145. Klaus Stark
  146. Kari Stefansson
  147. David-Alexandre Trégouët
  148. Jarmo Virtamo
  149. Lars Wallentin
  150. Nicholas Wareham
  151. Martina E Zimmermann
  152. Markku S Nieminen
  153. Christian Hengstenberg
  154. Manjinder S Sandhu
  155. Tomi Pastinen
  156. Ann-Christine Syvänen
  157. G Kees Hovingh
  158. George Dedoussis
  159. Paul W Franks
  160. Terho Lehtimäki
  161. Andres Metspalu
  162. Pierre A Zalloua
  163. Agneta Siegbahn
  164. Stefan Schreiber
  165. Samuli Ripatti
  166. Stefan S Blankenberg
  167. Markus Perola
  168. Robert Clarke
  169. Bernhard O Boehm
  170. Christopher O'Donnell
  171. Muredach P Reilly
  172. Winfried März
  173. Rory Collins
  174. Sekar Kathiresan
  175. Anders Hamsten
  176. Jaspal S Kooner
  177. Unnur Thorsteinsdottir
  178. John Danesh
  179. Colin N A Palmer
  180. Robert Roberts
  181. Hugh Watkins
  182. Heribert Schunkert
  183. Nilesh J Samani

Consortia

The CARDIoGRAMplusC4D Consortium

DIAGRAM Consortium

CARDIOGENICS Consortium

MuTHER Consortium

Wellcome Trust Case Control Consortium

Contributions

Writing committee: P. Deloukas, S. Kanoni, C.W., M.F., T.L.A., J.R.T., E.I., D. Saleheen, J.E., M.P. Reilly, R. Collins, S. Kathiresan, A.H., U.T., J.S.K., J.D., C.N.A.P., R.R., H.W., H.S. and N.J.S.Steering committee: P. Deloukas, S. Kanoni, C.W., M.F., T.L.A., J.R.T., E.I., D. Saleheen, J.E., M.P. Reilly, R. Collins, S. Kathiresan, A.H., U.T., J.S.K., J.D., C.N.A.P., R.R., H.W., H.S., N.J.S., S.S.B., B.O.B., J.C.C., R. Clarke, G.D., P.W.F., C.H., G.K.H., Jong-Young Lee, T.L., W.M., A.M., M.S.N., C.O., M.P., S. Ripatti, M.S.S., S.S., A. Siegbahn, C.J.W. and P.A.Z.Analysis committee: B.A.G., K. Stirrups, I.R.K., J.-B.C., Å.J., T.E., L.F., A.G., A.S. Havulinna, W.K.H., J.C.H., N.E., M.E.K., K. Kristiansson, P.L., L.-P.L., S. Rafelt, D. Shungin, R.J.S., G. Thorleifsson, E.T., N.V.Z., B.F.V., L.L.W., W.Z. and A.Z.Genotyping: D. Absher, I.B., C.B., S.C.-B., DIAGRAM Consortium, N.E.M., K.F., P.F., B.G., L.G., S.G., J.H., B.-G.H., S.E.H., T.K., J.W.K., C. Langenberg, C. Langford, M.I.M., M.M.-N., K.N., J.F.P., S. Rosinger, D.R., M.P. Rumpf, A. Schäfer, A.F.R.S., P.J.W. and Wellcome Trust Case Control Consortium.Array design: H.M.K. and N.W.R.Functional analyses: E.G., P.E., A.F.-C., A.L., O.M., S.M., MuTHER Consortium, T.-P.Y., A.H.G., E.S., T.P. and A.-C.S.Samples and phenotyping: (ADVANCE) A.S.G., C.I. and T.Q.; (AMC-PAS/SANQUIN) C.E.v.d.S. and H.B.; (Angio-Lüb/KORA) P. Diemert; (CADomics) P.S.W.; (CARDIOGENICS) F.C. and W.H.O.; (CHARGE) E.B., A.L.C., A.D. and V.G.; (Corogene) M.-L.L. and J.S.; (deCODE) G. Thorgeirsson, H.H. and K. Stefansson; (EPIC-NORFOLK) N.W.; (Estonian Biobank) E.M.; (FGENTCARD) D.G.; (FINCAVAS) M.K.; (FINRISK 2007/DILGOM) V.S.; (FRISCII) L.W.; (GerMIFS) T.I., C.M., K. Stark and M.E.Z.; (GLACIER) G.H.; (GoDARTS Dundee) A.S.F.D. and A.D.M.; (HPS) S.P.; (Korean GenRIC) Y.J., H.-S.K., Ji-Young Lee and J.E.P.; (LOLIPOP) S.-T.T.; (LURIC/AtheroRemo) R.L. and W. Koenig; (METSIM) J.K., M.B. and M.L.; (MIGen) R.D.; (MORGAM) K. Kuulasmaa, J.V., P.A., D. Arveiler., J.F., D.-A.T., N.K., A.P., P.B., M.M.F., A.E. and F.K.; (Ottawa Heart Genomics Study) G.A.W., S.L.H. and S.H.S.; (PennCATH/MedStar) S.E.E. and D.J.R.; (Pfizer-Broad-Malmo) D. Altshuler and D.C.; (PIVUS/Swedish Twin Registry) C.S., L.L. and N.L.P.; (PROMIS) A.R.; (SHEEP-SCARF) K.L. and U.d.F.; (THISEAS) M.D., G.K.; (Ulm-EMIL) W. Kratzer; and (WTCCC) A.J.B., P.S.B., M.S. and A.S. Hall.

Corresponding authors

Correspondence toPanos Deloukas orNilesh J Samani.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Additional information

A list of members and affiliations appears in theSupplementary Note.

A list of members and affiliations appears in theSupplementary Note.

A list of members and affiliations appears in theSupplementary Note.

A list of members and affiliations appears in theSupplementary Note.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–7, Supplementary Tables 1–8 and Supplementary Note (PDF 2619 kb)

Supplementary Table 9

SNPs at an FDR⩽5% and LD threshold of r2 < 0.2 used in estimating heritability (XLS 88 kb)

Supplementary Table 10

Network molecules (XLS 114 kb)

Rights and permissions

About this article

Cite this article

The CARDIoGRAMplusC4D Consortium., Deloukas, P., Kanoni, S.et al. Large-scale association analysis identifies new risk loci for coronary artery disease.Nat Genet45, 25–33 (2013). https://doi.org/10.1038/ng.2480

Download citation

This article is cited by

Access through your institution
Buy or subscribe

Advertisement

Search

Advanced search

Quick links

Nature Briefing

Sign up for theNature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox.Sign up for Nature Briefing
[8]ページ先頭
©2009-2026 Movatter.jp