A comprehensive 1000 Genomes–based genome-wide association meta-analysis of coronary artery disease View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-10

AUTHORS

CAIoGRAMplusC4D Consortium, Majid Nikpay, Anuj Goel, Hong-Hee Won, Leanne M Hall, Christina Willenborg, Stavroula Kanoni, Danish Saleheen, Theodosios Kyriakou, Christopher P Nelson, Jemma C Hopewell, Thomas R Webb, Lingyao Zeng, Abbas Dehghan, Maris Alver, Sebastian M Armasu, Kirsi Auro, Andrew Bjonnes, Daniel I Chasman, Shufeng Chen, Ian Ford, Nora Franceschini, Christian Gieger, Christopher Grace, Stefan Gustafsson, Jie Huang, Shih-Jen Hwang, Yun Kyoung Kim, Marcus E Kleber, Wai Lau, Xiangfeng Lu, Yingchang Lu, Leo-Pekka Lyytikäinen, Evelin Mihailov, Alanna C Morrison, Natalia Pervjakova, Liming Qu, Lynda M Rose, Elias Salfati, Richa Saxena, Markus Scholz, Albert V Smith, Emmi Tikkanen, Andre Uitterlinden, Xueli Yang, Weihua Zhang, Wei Zhao, Mariza de Andrade, Paul S de Vries, Natalie R van Zuydam, Sonia S Anand, Lars Bertram, Frank Beutner, George Dedoussis, Philippe Frossard, Dominique Gauguier, Alison H Goodall, Omri Gottesman, Marc Haber, Bok-Ghee Han, Jianfeng Huang, Shapour Jalilzadeh, Thorsten Kessler, Inke R König, Lars Lannfelt, Wolfgang Lieb, Lars Lind, Cecilia M Lindgren, Marja-Liisa Lokki, Patrik K Magnusson, Nadeem H Mallick, Narinder Mehra, Thomas Meitinger, Fazal-ur-Rehman Memon, Andrew P Morris, Markku S Nieminen, Nancy L Pedersen, Annette Peters, Loukianos S Rallidis, Asif Rasheed, Maria Samuel, Svati H Shah, Juha Sinisalo, Kathleen E Stirrups, Stella Trompet, Laiyuan Wang, Khan S Zaman, Diego Ardissino, Eric Boerwinkle, Ingrid B Borecki, Erwin P Bottinger, Julie E Buring, John C Chambers, Rory Collins, L Adrienne Cupples, John Danesh, Ilja Demuth, Roberto Elosua, Stephen E Epstein, Tõnu Esko, Mary F Feitosa, Oscar H Franco, Maria Grazia Franzosi, Christopher B Granger, Dongfeng Gu, Vilmundur Gudnason, Alistair S Hall, Anders Hamsten, Tamara B Harris, Stanley L Hazen, Christian Hengstenberg, Albert Hofman, Erik Ingelsson, Carlos Iribarren, J Wouter Jukema, Pekka J Karhunen, Bong-Jo Kim, Jaspal S Kooner, Iftikhar J Kullo, Terho Lehtimäki, Ruth J F Loos, Olle Melander, Andres Metspalu, Winfried März, Colin N Palmer, Markus Perola, Thomas Quertermous, Daniel J Rader, Paul M Ridker, Samuli Ripatti, Robert Roberts, Veikko Salomaa, Dharambir K Sanghera, Stephen M Schwartz, Udo Seedorf, Alexandre F Stewart, David J Stott, Joachim Thiery, Pierre A Zalloua, Christopher J O'Donnell, Muredach P Reilly, Themistocles L Assimes, John R Thompson, Jeanette Erdmann, Robert Clarke, Hugh Watkins, Sekar Kathiresan, Ruth McPherson, Panos Deloukas, Heribert Schunkert, Nilesh J Samani, Martin Farrall

ABSTRACT

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. More... »

PAGES

1121-1130

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  • Journal

    TITLE

    Nature Genetics

    ISSUE

    10

    VOLUME

    47

    Author Affiliations

  • University of Ottawa
  • Wellcome Centre for Human Genetics
  • Harvard University
  • University of Leicester
  • German Centre for Cardiovascular Research
  • Queen Mary University of London
  • Center for Non-Communicable Diseases
  • Glenfield Hospital
  • University of Oxford
  • Erasmus University Medical Center
  • University of Tartu
  • Mayo Clinic
  • University of Helsinki
  • Massachusetts General Hospital
  • Peking Union Medical College Hospital
  • University of Glasgow
  • University of North Carolina at Chapel Hill
  • Uppsala University
  • Wellcome Sanger Institute
  • Boston University
  • Korea National Institute of Health
  • Heidelberg University
  • Icahn School of Medicine at Mount Sinai
  • University of Tampere
  • The University of Texas Health Science Center at Houston
  • University of Pennsylvania
  • Brigham and Women's Hospital
  • Stanford University
  • Leipzig University
  • University of Iceland
  • Imperial College London
  • University of Dundee
  • McMaster University
  • Harokopio University
  • Centre de Recherche des Cordeliers
  • Lebanese American University
  • Rechts der Isar Hospital
  • University of Lübeck
  • Kiel University
  • Broad Institute
  • Karolinska Institute
  • Punjab Institute of Cardiology
  • All India Institute of Medical Sciences
  • Technical University Munich
  • University of Liverpool
  • Helsinki University Central Hospital
  • National and Kapodistrian University of Athens
  • Duke Medical Center
  • University of Cambridge
  • Leiden University Medical Center
  • National Institute of Cardiovascular Diseases
  • Ospedale di Parma
  • Baylor College of Medicine
  • Washington University in St. Louis
  • Imperial College Healthcare NHS Trust
  • Charité
  • Institut Hospital del Mar d'Investigacions Mèdiques
  • MedStar Washington Hospital Center
  • Mario Negri Institute for Pharmacological Research
  • University of Leeds
  • National Institutes of Health
  • Cleveland Clinic
  • Kaiser Permanente
  • Netherlands Heart Institute
  • Medical University of Graz
  • National Institute for Health and Welfare
  • University of Oklahoma Health Sciences Center
  • University of Washington
  • University Medical Center Hamburg-Eppendorf
  • University Hospital Leipzig
  • King Abdulaziz University
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.3396

    DOI

    http://dx.doi.org/10.1038/ng.3396

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1034378235

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/26343387


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