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

Panos Deloukas; Stavroula Kanoni; Christina Willenborg; Martin Farrall; Themistocles L. Assimes; John R. Thompson; Erik Ingelsson; Danish Saleheen; Jeanette Erdmann; Benjamin A. Goldstein; Kathleen Stirrups; Inke R. Koenig; Jean-Baptiste Cazier; Asa Johansson; Alistair S. Hall; Jong-Young Lee; Cristen J. Willer; John C. Chambers; Tonu Esko; Lasse Folkersen; Anuj Goel; Elin Grundberg; Aki S. Havulinna; Weang K. Ho; Jemma C. Hopewell; Niclas Eriksson; Marcus E. Kleber; Kati Kristiansson; Per Lundmark; Leo-Pekka Lyytikainen; Suzanne Rafelt; Dmitry Shungin; Rona J. Strawbridge; Gudmar Thorleifsson; Emmi Tikkanen; Natalie Van Zuydam; Benjamin F. Voight; Lindsay L. Waite; Weihua Zhang; Andreas Ziegler; Devin Absher; David Altshuler; Anthony J. Balmforth; Ines Barroso; Peter S. Braund; Christof Burgdorf; Simone Claudi-Boehm; David Cox; Maria Dimitriou; Ron Do; Alex S. F. Doney; NourEddine El Mokhtari; Per Eriksson; Krista Fischer; Pierre Fontanillas; Anders Franco-Cereceda; Bruna Gigante; Leif Groop; Stefan Gustafsson; Joerg Hager; Goran Hallmans; Bok-Ghee Han; Sarah E. Hunt; Hyun M. Kang; Thomas Illig; Thorsten Kessler; Joshua W. Knowles; Genovefa Kolovou; Johanna Kuusisto; Claudia Langenberg; Cordelia Langford; Karin Leander; Marja-Liisa Lokki; Anders Lundmark; Mark I. McCarthy; Christa Meisinger; Olle Melander; Evelin Mihailov; Seraya Maouche; Andrew D. Morris; Martina Mueller-Nurasyid; Kjell Nikus; John F. Peden; N. William Rayner; Asif Rasheed; Silke Rosinger; Diana Rubin; Moritz P. Rumpf; Arne Schaefer; Mohan Sivananthan; Ci Song; Alexandre F. R. Stewart; Sian-Tsung Tan; Gudmundur Thorgeirsson; C. Ellen van der Schoot; Peter J. Wagner; George A. Wells; Philipp S. Wild; Tsun-Po Yang; Philippe Amouyel; Dominique Arveiler; Hanneke Basart; Michael Boehnke; Eric Boerwinkle; Paolo Brambilla; Francois Cambien; Adrienne L. Cupples; Ulf de Faire; Abbas Dehghan; Patrick Diemert; Stephen E. Epstein; Alun Evans; Marco M. Ferrario; Jean Ferrieres; Dominique Gauguier; Alan S. Go; Alison H. Goodall; Villi Gudnason; Stanley L. Hazen; Hilma Holm; Carlos Iribarren; Yangsoo Jang; Mika Kahonen; Frank Kee; Hyo-Soo Kim; Norman Klopp; Wolfgang Koenig; Wolfgang Kratzer; Kari Kuulasmaa; Markku Laakso; Reijo Laaksonen; Ji-Young Lee; Lars Lind; Willem H. Ouwehand; Sarah Parish; Jeong E. Park; Nancy L. Pedersen; Annette Peters; Thomas Quertermous; Daniel J. Rader; Veikko Salomaa; Eric Schadt; Svati H. Shah; Juha Sinisalo; Klaus Stark; Kari Stefansson; David-Alexandre Tregouet; Jarmo Virtamo; Lars Wallentin; Nicholas Wareham; Martina E. Zimmermann; Markku S. Nieminen; Christian Hengstenberg; Manjinder S. Sandhu; Tomi Pastinen; Ann-Christine Syvanen; G. Kees Hovingh; George Dedoussis; Paul W. Franks; Terho Lehtimaki; Andres Metspalu; Pierre A. Zalloua; Agneta Siegbahn; Stefan Schreiber; Samuli Ripatti; Stefan S. Blankenberg; Markus Perola; Robert Clarke; Bernhard O. Boehm; Christopher O'Donnell; Muredach P. Reilly; Winfried Maerz; Rory Collins; Sekar Kathiresan; Anders Hamsten; Jaspal S. Kooner; Unnur Thorsteinsdottir; John Danesh; Colin N. A. Palmer; Robert Roberts; Hugh Watkins; Heribert Schunkert; Nilesh J. Samani; CARDIOGENENICS Consortium

doi:10.1038/ng.2480

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

Journal article

Peer reviewed

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

Panos Deloukas, Stavroula Kanoni, Christina Willenborg, Martin Farrall, Themistocles L. Assimes, John R. Thompson, Erik Ingelsson, Danish Saleheen, Jeanette Erdmann, Benjamin A. Goldstein, …

Nature genetics, Vol.45(1), pp.25-U52

01/01/2013

DOI: https://doi.org/10.1038/ng.2480

PMCID: PMC3679547

PMID: 23202125

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

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 (r(2) < 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.

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Title: Large-scale association analysis identifies new risk loci for coronary artery disease
Creators - without role: Panos Deloukas - Wellcome Sanger Institute
Stavroula Kanoni - Wellcome Sanger Institute
Christina Willenborg - University of Lübeck
Martin Farrall - University of Oxford
Themistocles L. Assimes - Stanford University
John R. Thompson - University of Leicester
Erik Ingelsson - Karolinska Institutet
Danish Saleheen - Ctr Noncommunicable Dis, Karachi, Pakistan
Jeanette Erdmann - University of Lübeck
Benjamin A. Goldstein - Stanford University
Kathleen Stirrups - Wellcome Sanger Institute
Inke R. Koenig - University of Lübeck
Jean-Baptiste Cazier - University of Oxford
Asa Johansson - Uppsala University
Alistair S. Hall - University of Leeds
Jong-Young Lee - Korea Ctr Dis Control & Prevent, Korea Natl Inst Hlth, Ctr Genome Sci, Yeonje Ri, Chungwon Gun, South Korea
Cristen J. Willer - College Station Medical Center
John C. Chambers - University of London
Tonu Esko - University of Tartu
Lasse Folkersen - Karolinska Institutet
Anuj Goel - University of Oxford
Elin Grundberg - Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England
Aki S. Havulinna - Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland
Weang K. Ho - College Station Medical Center
Jemma C. Hopewell - University of Oxford
Niclas Eriksson - Uppsala University
Marcus E. Kleber - University of Mannheim
Kati Kristiansson - Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland
Per Lundmark - Uppsala University
Leo-Pekka Lyytikainen - Tampere University
Suzanne Rafelt - University of Leicester
Dmitry Shungin - Lund University
Rona J. Strawbridge - Karolinska Institutet
Gudmar Thorleifsson - deCODE Genet, Reykjavik, Iceland
Emmi Tikkanen - University of Helsinki
Natalie Van Zuydam - University of Dundee
Benjamin F. Voight - Univ Penn, Dept Pharmacol, Philadelphia, PA 19104 USA
Lindsay L. Waite - HudsonAlpha Inst Biotechnol, Huntsville, AL USA
Weihua Zhang - University of London
Andreas Ziegler - University of Lübeck
Devin Absher - HudsonAlpha Inst Biotechnol, Huntsville, AL USA
David Altshuler - Broad Institute
Anthony J. Balmforth - University of Leeds
Ines Barroso - Wellcome Sanger Institute
Peter S. Braund - University of Leicester
Christof Burgdorf - Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany
Simone Claudi-Boehm - University of Ulm
David Cox - Pfizer
Maria Dimitriou - Harokopio University of Athens
Ron Do - Broad Institute
Alex S. F. Doney - University of Dundee
NourEddine El Mokhtari - College Station Medical Center
Per Eriksson - Karolinska Institutet
Krista Fischer - University of Tartu
Pierre Fontanillas - Broad Institute
Anders Franco-Cereceda - Karolinska Institutet
Bruna Gigante - Karolinska Institutet
Leif Groop - Malmö University
Stefan Gustafsson - Karolinska Institutet
Joerg Hager - CEA, Genom Inst, Natl Genotyping Ctr, Paris, France
Goran Hallmans - Umeå University
Bok-Ghee Han - Korea Ctr Dis Control & Prevent, Korea Natl Inst Hlth, Ctr Genome Sci, Yeonje Ri, Chungwon Gun, South Korea
Sarah E. Hunt - Wellcome Sanger Institute
Hyun M. Kang - Biostat
Thomas Illig - Supreme Council Of Health
Thorsten Kessler - Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany
Joshua W. Knowles - Stanford University
Genovefa Kolovou - Onassis Cardiac Surg Ctr 356, Cardiol Dept 1, Athens, Greece
Johanna Kuusisto - University of Eastern Finland
Claudia Langenberg - Massachusetts Rehabilitation Commission
Cordelia Langford - Wellcome Sanger Institute
Karin Leander - Karolinska Institutet
Marja-Liisa Lokki - University of Helsinki
Anders Lundmark - Uppsala University
Mark I. McCarthy - University of Oxford
Christa Meisinger - Helmholtz Zentrum München
Olle Melander - Malmö University
Evelin Mihailov - University of Tartu
Seraya Maouche - Université Paris Cité
Andrew D. Morris - University of Dundee
Martina Mueller-Nurasyid - College Station Medical Center
Kjell Nikus - Tampere University
John F. Peden - University of Oxford
N. William Rayner - University of Oxford
Asif Rasheed - University of Cambridge
Silke Rosinger - University of Ulm
Diana Rubin - College Station Medical Center
Moritz P. Rumpf - Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany
Arne Schaefer - Univ Kiel, Inst Klin Mol Biol, Kiel, Germany
Mohan Sivananthan - University of Leeds
Ci Song - Karolinska Institutet
Alexandre F. R. Stewart - University of Ottawa
Sian-Tsung Tan - University of London
Gudmundur Thorgeirsson - University of Iceland
C. Ellen van der Schoot - Sanquin
Peter J. Wagner - University of Helsinki
George A. Wells - University of Ottawa
Philipp S. Wild - Johannes Gutenberg University Mainz
Tsun-Po Yang - Wellcome Sanger Institute
Philippe Amouyel - University of Lille
Dominique Arveiler - University of Strasbourg
Hanneke Basart - University of Amsterdam
Michael Boehnke - Biostat
Eric Boerwinkle - Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA
Paolo Brambilla - University of Milano-Bicocca
Francois Cambien - Université Paris Cité
Adrienne L. Cupples - Boston University
Ulf de Faire - Karolinska Institutet
Abbas Dehghan - Erasmus MC
Patrick Diemert - Univ Heart Ctr Hamburg, Clin Gen & Intervent Cardiol, Hamburg, Germany
Stephen E. Epstein - Washington Hosp Ctr, Cardiovasc Res Inst, Washington, DC 20010 USA
Alun Evans - Queens University
Marco M. Ferrario - University of Insubria
Jean Ferrieres - Supreme Council Of Health
Dominique Gauguier - University of Oxford
Alan S. Go - Kaiser Permanente
Alison H. Goodall - University of Leicester
Villi Gudnason - University of Iceland
Stanley L. Hazen - Cleveland Clin, Lerner Res Inst, Cleveland, OH 44106 USA
Hilma Holm - deCODE Genet, Reykjavik, Iceland
Carlos Iribarren - Kaiser Permanente
Yangsoo Jang - Yonsei University
Mika Kahonen - Tampere University
Frank Kee - Queens University
Hyo-Soo Kim - College Station Medical Center
Norman Klopp - Supreme Council Of Health
Wolfgang Koenig - University of Ulm
Wolfgang Kratzer - Tampere University
Kari Kuulasmaa - Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland
Markku Laakso - University of Eastern Finland
Reijo Laaksonen - Tampere University
Ji-Young Lee - Korea Ctr Dis Control & Prevent, Korea Natl Inst Hlth, Ctr Genome Sci, Yeonje Ri, Chungwon Gun, South Korea
Lars Lind - Uppsala University
Willem H. Ouwehand - Wellcome Sanger Institute
Sarah Parish - University of Oxford
Jeong E. Park - Sungkyunkwan University
Nancy L. Pedersen - Karolinska Institutet
Annette Peters - Helmholtz Zentrum München
Thomas Quertermous - Stanford University
Daniel J. Rader - Supreme Council Of Health
Veikko Salomaa - Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland
Eric Schadt - Supreme Council Of Health
Svati H. Shah - Duke University
Juha Sinisalo - College Station Medical Center
Klaus Stark - College Station Medical Center
Kari Stefansson - deCODE Genet, Reykjavik, Iceland
David-Alexandre Tregouet - Université Paris Cité
Jarmo Virtamo - Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland
Lars Wallentin - Uppsala University
Nicholas Wareham - Massachusetts Rehabilitation Commission
Martina E. Zimmermann - College Station Medical Center
Markku S. Nieminen - College Station Medical Center
Christian Hengstenberg - College Station Medical Center
Manjinder S. Sandhu - Wellcome Sanger Institute
Tomi Pastinen - McGill University
Ann-Christine Syvanen - Uppsala University
G. Kees Hovingh - University of Amsterdam
George Dedoussis - Harokopio University of Athens
Paul W. Franks - Lund University
Terho Lehtimaki - Tampere University
Andres Metspalu - University of Tartu
Pierre A. Zalloua - Lebanese Amer Univ, Beirut, Lebanon
Agneta Siegbahn - Uppsala University
Stefan Schreiber - Univ Kiel, Inst Klin Mol Biol, Kiel, Germany
Samuli Ripatti - Wellcome Sanger Institute
Stefan S. Blankenberg - Univ Heart Ctr Hamburg, Clin Gen & Intervent Cardiol, Hamburg, Germany
Markus Perola - Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland
Robert Clarke - University of Oxford
Bernhard O. Boehm - University of Ulm
Christopher O'Donnell - Erasmus MC
Muredach P. Reilly - Supreme Council Of Health
Winfried Maerz - University of Mannheim
Rory Collins - University of Oxford
Sekar Kathiresan - Broad Institute
Anders Hamsten - Karolinska Institutet
Jaspal S. Kooner - University of London
Unnur Thorsteinsdottir - deCODE Genet, Reykjavik, Iceland
John Danesh - University of Cambridge
Colin N. A. Palmer - University of Dundee
Robert Roberts - University of Ottawa
Hugh Watkins - University of Oxford
Heribert Schunkert - Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany
Nilesh J. Samani - University of Leicester
CARDIOGENENICS Consortium
Publication Details: Nature genetics, Vol.45(1), pp.25-U52
Publisher: Springer Nature
Number of pages: 11
Grant note: Merck; Merck & Company G0601261; MC_U137686857; G0700931; G0801566; G0601966 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) MC_CF023241; G0700931; MC_UU_12015/1; G0601261; MC_U137686857; G0801566; G0601966 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) PG/08/094/26019; RG/08/014/24067; RG/09/012/28096 / British Heart Foundation British Heart Foundation (BHF) Centre of Research Excellence; British Heart Foundation NF-SI-0611-10170; RP-PG-0310-1002; NF-SI-0611-10099 / National Institute for Health Research; National Institute for Health Research (NIHR)
Identifiers: 9937708508331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article