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A comprehensive 1,000 Genomes-based genome-wide association meta-analysis of coronary artery disease.
Nikpay, Majid; Goel, Anuj; Won, Hong-Hee; Hall, Leanne M; Willenborg, Christina; Kanoni, Stavroula; Saleheen, Danish; Kyriakou, Theodosios; Nelson, Christopher P; Hopewell, Jemma C; Webb, Thomas R; Zeng, Lingyao; Dehghan, Abbas; Alver, Maris; Armasu, Sebastian M; Auro, Kirsi; Bjonnes, Andrew; Chasman, Daniel I; Chen, Shufeng; Ford, Ian; Franceschini, Nora; Gieger, Christian; Grace, Christopher; Gustafsson, Stefan; Huang, Jie; Hwang, Shih-Jen; Kim, Yun Kyoung; Kleber, Marcus E; Lau, King Wai; Lu, Xiangfeng; Lu, Yingchang; Lyytikäinen, Leo-Pekka; Mihailov, Evelin; Morrison, Alanna C; Pervjakova, Natalia; Qu, Liming; Rose, Lynda M; Salfati, Elias; Saxena, Richa; Scholz, Markus; Smith, Albert V; Tikkanen, Emmi; Uitterlinden, Andre; Yang, Xueli; Zhang, Weihua; Zhao, Wei; de Andrade, Mariza; de Vries, Paul S; van Zuydam, Natalie R; Anand, Sonia S.
Afiliación
  • Nikpay M; Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa Heart Institute, Ottawa, Canada.
  • Goel A; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
  • Won HH; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Hall LM; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts, USA.
  • Willenborg C; Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
  • Kanoni S; Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.
  • Saleheen D; Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
  • Kyriakou T; Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
  • Nelson CP; Institut für Integrative und Experimentelle Genomik, Universität zu Lübeck, Lübeck, Germany.
  • Hopewell JC; DZHK (German Research Center for Cardiovascular Research) partner site Hamburg-Lübeck-Kiel, Lübeck, Germany.
  • Webb TR; William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
  • Zeng L; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Dehghan A; Center for Non-Communicable Diseases, Karachi, Pakistan.
  • Alver M; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
  • Armasu SM; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Auro K; Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
  • Bjonnes A; NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK.
  • Chasman DI; CTSU, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • Chen S; Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
  • Ford I; NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK.
  • Franceschini N; Deutsches Herzzentrum München, Technische Universität München, München, Germany.
  • Gieger C; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, München, Germany.
  • Grace C; Department of Epidemiology, Erasmus University Medical center, Rotterdam, The Netherlands.
  • Gustafsson S; Estonian Genome Center, University of Tartu, Tartu, Estonia.
  • Huang J; Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
  • Hwang SJ; Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
  • Kim YK; Department of Health, National Institute for Health and Welfare, Helsinki, Finland.
  • Kleber ME; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
  • Lau KW; Diabetes & Obesity Research Program, University of Helsinki, Helsinki, Finland.
  • Lu X; Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts, USA.
  • Lu Y; Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA.
  • Lyytikäinen LP; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
  • Mihailov E; Harvard Medical School, Boston, Massachusetts, USA.
  • Morrison AC; State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  • Pervjakova N; Robertson Center for Biostatistics, University of Glasgow, Glasgow, UK.
  • Qu L; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA.
  • Rose LM; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, München, Germany.
  • Salfati E; Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
  • Saxena R; Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
  • Scholz M; Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
  • Smith AV; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
  • Tikkanen E; Molecular Epidemiology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
  • Uitterlinden A; Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
  • Yang X; Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK.
  • Zhang W; National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA.
  • Zhao W; Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.
  • de Andrade M; Center for Genome Science, Korea National Institute of Health, Chungcheongbuk-do, Korea.
  • de Vries PS; Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, University of Heidelberg, Mannheim, Germany.
  • van Zuydam NR; CTSU, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
  • Anand SS; State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Nat Genet ; 47(10): 1121-1130, 2015 Oct.
Article en En | MEDLINE | ID: mdl-26343387
Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of ∼185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 million low-frequency (0.005 < MAF < 0.05) variants. In addition to confirming most known CAD-associated loci, we identified ten new loci (eight additive and two recessive) that contain candidate causal genes newly implicating biological processes in vessel walls. We observed intralocus allelic heterogeneity but little evidence of low-frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD, showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de la Arteria Coronaria / Genoma Humano / Estudio de Asociación del Genoma Completo Tipo de estudio: Risk_factors_studies / Systematic_reviews Límite: Humans Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2015 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de la Arteria Coronaria / Genoma Humano / Estudio de Asociación del Genoma Completo Tipo de estudio: Risk_factors_studies / Systematic_reviews Límite: Humans Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2015 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos