A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease

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; King Wai Lau; Xiangfeng Lu; Yingchang Lu; Leo-Pekka Lyytikainen; 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. Koenig; 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; Tonu 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 Lehtimaki; Ruth J. F. Loos; Olle Melander; Andres Metspalu; Winfried Maerz; 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; CARDIoGRAMplusC4D Consortium

doi:10.1038/ng.3396

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A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease

Journal article

Peer reviewed

A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease

Majid Nikpay, Anuj Goel, Hong-Hee Won, Leanne M. Hall, Christina Willenborg, Stavroula Kanoni, Danish Saleheen, Theodosios Kyriakou, Christopher P. Nelson, Jemma C. Hopewell, …

Nature genetics, Vol.47(10), pp.1121-1130

01/10/2015

DOI: https://doi.org/10.1038/ng.3396

PMCID: PMC4589895

PMID: 26343387

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

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 similar to 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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Title: A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease
Creators - without role: Majid Nikpay - University of Ottawa
Anuj Goel - University of Oxford
Hong-Hee Won - Harvard University
Leanne M. Hall - University of Leicester
Christina Willenborg - University of Lübeck
Stavroula Kanoni - Queen Mary University of London
Danish Saleheen - Supreme Council Of Health
Theodosios Kyriakou - University of Oxford
Christopher P. Nelson - University of Leicester
Jemma C. Hopewell - University of Oxford
Thomas R. Webb - University of Leicester
Lingyao Zeng - Tech Univ Munich, Deutsches Herzzentrum Munchen, D-80290 Munich, Germany
Abbas Dehghan - College Station Medical Center
Maris Alver - University of Tartu
Sebastian M. Armasu - Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN USA
Kirsi Auro - Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland
Andrew Bjonnes - Harvard University
Daniel I. Chasman - Brigham and Women's Hospital
Shufeng Chen - College Station Medical Center
Ian Ford - University of Glasgow
Nora Franceschini - Supreme Council Of Health
Christian Gieger - DZHK German Ctr Cardiovasc Res, Munich, Germany
Christopher Grace - University of Oxford
Stefan Gustafsson - Uppsala University
Jie Huang - Wellcome Sanger Institute
Shih-Jen Hwang - Framingham Heart Study
Yun Kyoung Kim - Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea
Marcus E. Kleber - Heidelberg University
King Wai Lau - University of Oxford
Xiangfeng Lu - College Station Medical Center
Yingchang Lu - Supreme Council Of Health
Leo-Pekka Lyytikainen - Fimlab
Evelin Mihailov - University of Tartu
Alanna C. Morrison - Supreme Council Of Health
Natalia Pervjakova - University of Tartu
Liming Qu - Biostat
Lynda M. Rose - Brigham and Women's Hospital
Elias Salfati - Stanford University
Richa Saxena - Harvard University
Markus Scholz - MED Institute
Albert V. Smith - Iceland Heart Assoc, Kopavogur, Iceland
Emmi Tikkanen - University of Helsinki
Andre Uitterlinden - College Station Medical Center
Xueli Yang - College Station Medical Center
Weihua Zhang - University of London
Wei Zhao - Supreme Council Of Health
Mariza de Andrade - Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN USA
Paul S. de Vries - College Station Medical Center
Natalie R. van Zuydam - University of Oxford
Sonia S. Anand - McMaster University
Lars Bertram - University of Lübeck
Frank Beutner - LIFE Res Ctr Civilizat Dis, Leipzig, Germany
George Dedoussis - Harokopio University of Athens
Philippe Frossard - Ctr Noncommunicable Dis, Karachi, Pakistan
Dominique Gauguier - Inserm
Alison H. Goodall - Glenfield Hosp, NIHR, Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England
Omri Gottesman - Supreme Council Of Health
Marc Haber - Supreme Council Of Health
Bok-Ghee Han - Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea
Jianfeng Huang - College Station Medical Center
Shapour Jalilzadeh - University of Oxford
Thorsten Kessler - Tech Univ Munich, Deutsches Herzzentrum Munchen, D-80290 Munich, Germany
Inke R. Koenig - DZHK German Res Ctr Cardiovasc Res, Lubeck, Germany
Lars Lannfelt - Uppsala University
Wolfgang Lieb - Univ Kiel, Inst Epidemiol, Kiel, Germany
Lars Lind - Uppsala University
Cecilia M. Lindgren - University of Oxford
Marja-Liisa Lokki - University of Helsinki
Patrik K. Magnusson - Karolinska Institutet
Nadeem H. Mallick - Punjab Inst Cardiol, Lahore, Pakistan
Narinder Mehra - College Station Medical Center
Thomas Meitinger - DZHK German Ctr Cardiovasc Res, Munich, Germany
Fazal-ur-Rehman Memon - Red Crescent Inst Cardiol, Hyderabad, Andhra Pradesh, Pakistan
Andrew P. Morris - University of Oxford
Markku S. Nieminen - University of Helsinki
Nancy L. Pedersen - Karolinska Institutet
Annette Peters - DZHK German Ctr Cardiovasc Res, Munich, Germany
Loukianos S. Rallidis - National and Kapodistrian University of Athens
Asif Rasheed - Ctr Noncommunicable Dis, Karachi, Pakistan
Maria Samuel - Ctr Noncommunicable Dis, Karachi, Pakistan
Svati H. Shah - Duke University
Juha Sinisalo - University of Helsinki
Kathleen E. Stirrups - Queen Mary University of London
Stella Trompet - Leiden University
Laiyuan Wang - College Station Medical Center
Khan S. Zaman - Natl Inst Cardiovasc Dis, Karachi, Pakistan
Diego Ardissino - University of Parma
Eric Boerwinkle - Supreme Council Of Health
Ingrid B. Borecki - Supreme Council Of Health
Erwin P. Bottinger - Supreme Council Of Health
Julie E. Buring - Brigham and Women's Hospital
John C. Chambers - University of London
Rory Collins - University of Oxford
L. Adrienne Cupples - Framingham Heart Study
John Danesh - Wellcome Sanger Institute
Ilja Demuth - Berlin Aging Study 2, Berlin, Germany
Roberto Elosua - College Station Medical Center
Stephen E. Epstein - MedStar Washington Hosp Ctr, MedStar Heart & Vasc Inst, Washington, DC USA
Tonu Esko - Harvard University
Mary F. Feitosa - Supreme Council Of Health
Oscar H. Franco - College Station Medical Center
Maria Grazia Franzosi - Mylan
Christopher B. Granger - Duke University
Dongfeng Gu - College Station Medical Center
Vilmundur Gudnason - Iceland Heart Assoc, Kopavogur, Iceland
Alistair S. Hall - University of Leeds
Anders Hamsten - Karolinska Institutet
Tamara B. Harris - NIA, Lab Epidemiol Demog & Biometry, US Natl Inst Hlth, Bethesda, MD 20892 USA
Stanley L. Hazen - College Station Medical Center
Christian Hengstenberg - Tech Univ Munich, Deutsches Herzzentrum Munchen, D-80290 Munich, Germany
Albert Hofman - College Station Medical Center
Erik Ingelsson - University of Oxford
Carlos Iribarren - Kaiser Permanente
J. Wouter Jukema - Leiden University
Pekka J. Karhunen - Fimlab
Bong-Jo Kim - Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea
Jaspal S. Kooner - Ealing Hosp Natl Hlth Serv NHS Trust, Dept Cardiol, Southall, Middx, England
Iftikhar J. Kullo - College Station Medical Center
Terho Lehtimaki - Fimlab
Ruth J. F. Loos - Supreme Council Of Health
Olle Melander - Lund University
Andres Metspalu - University of Tartu
Winfried Maerz - Heidelberg University
Colin N. Palmer - University of Dundee
Markus Perola - University of Tartu
Thomas Quertermous - Stanford University
Daniel J. Rader - Supreme Council Of Health
Paul M. Ridker - Brigham and Women's Hospital
Samuli Ripatti - University of Helsinki
Robert Roberts - University of Ottawa
Veikko Salomaa - Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland
Dharambir K. Sanghera - University of Oklahoma
Stephen M. Schwartz - Hutchinson
Udo Seedorf - Univ Med Ctr Hamburg Eppendorf, Ctr Dent & Oral Med, Dept Prosthet Dent, Hamburg, Germany
Alexandre F. Stewart - University of Ottawa
David J. Stott - University of Glasgow
Joachim Thiery - LIFE Res Ctr Civilizat Dis, Leipzig, Germany
Pierre A. Zalloua - Supreme Council Of Health
Christopher J. O'Donnell - Framingham Heart Study
Muredach P. Reilly
Themistocles L. Assimes - Stanford University
John R. Thompson - University of Leicester
Jeanette Erdmann - University of Lübeck
Robert Clarke - University of Oxford
Hugh Watkins - University of Oxford
Sekar Kathiresan - Harvard University
Ruth McPherson - University of Ottawa
Panos Deloukas - Queen Mary University of London
Heribert Schunkert - Tech Univ Munich, Deutsches Herzzentrum Munchen, D-80290 Munich, Germany
Nilesh J. Samani - University of Leicester
Martin Farrall - University of Oxford
CARDIoGRAMplusC4D Consortium
Publication Details: Nature genetics, Vol.47(10), pp.1121-1130
Publisher: NATURE PORTFOLIO
Number of pages: 12
Grant note: FS/14/55/30806; RG/08/014/24067; RG/14/5/30893 / British Heart Foundation MR/L003120/1; MR/L01629X/1 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) MR/L01629X/1; MR/L003120/1 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) NF-SI-0512-10165; NF-SI-0508-10235; NF-SI-0611-10170 / National Institute for Health Research; National Institute for Health Research (NIHR)
Identifiers: 9935697508331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article