Association analyses based on false discovery rate implicate new loci for coronary artery disease

Christopher P. Nelson; Anuj Goel; Adam S. Butterworth; Stavroula Kanoni; Tom R. Webb; Eirini Marouli; Lingyao Zeng; Ioanna Ntalla; Florence Y. Lai; Jemma C. Hopewell; Olga Giannakopoulou; Tao Jiang; Stephen E. Hamby; Emanuele Di Angelantonio; Themistocles L. Assimes; Erwin P. Bottinger; John C. Chambers; Robert Clarke; Colin N. A. Palmer; Richard M. Cubbon; Patrick Ellinor; Raili Ermel; Evangelos Evangelou; Paul W. Franks; Christopher Grace; Dongfeng Gu; Aroon D. Hingorani; Joanna M. M. Howson; Erik Ingelsson; Adnan Kastrati; Thorsten Kessler; Theodosios Kyriakou; Terho Lehtimaki; Xiangfeng Lu; Yingchang Lu; Winfried Maerz; Ruth McPherson; Andres Metspalu; Mar Pujades-Rodriguez; Arno Ruusalepp; Eric E. Schadt; Amand F. Schmidt; Michael J. Sweeting; Pierre A. Zalloua; Kamal AlGhalayini; Bernard D. Keavney; Jaspal S. Kooner; Ruth J. F. Loos; Riyaz S. Patel; Martin K. Rutter; Maciej Tomaszewski; Ioanna Tzoulaki; Eleftheria Zeggini; Jeanette Erdmann; George Dedoussis; Johan L. M. Bjorkegren; Heribert Schunkert; Martin Farrall; John Danesh; Nilesh J. Samani; Hugh Watkins; Panos Deloukas; Uk Biobank CardioMetab

doi:10.1038/ng.3913

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Association analyses based on false discovery rate implicate new loci for coronary artery disease

Journal article

Peer reviewed

Association analyses based on false discovery rate implicate new loci for coronary artery disease

Christopher P. Nelson, Anuj Goel, Adam S. Butterworth, Stavroula Kanoni, Tom R. Webb, Eirini Marouli, Lingyao Zeng, Ioanna Ntalla, Florence Y. Lai, Jemma C. Hopewell, …

Nature genetics, Vol.49(9), pp.1385-1391

01/09/2017

DOI: https://doi.org/10.1038/ng.3913

PMID: 28714975

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

Genome-wide association studies (GWAS) in coronary artery disease (CAD) had identified 66 loci at 'genome-wide significance' (P < 5 x 10(-8)) at the time of this analysis, but a much larger number of putative loci at a false discovery rate (FDR) of 5% (refs. 1-4). Here we leverage an interim release of UK Biobank (UKBB) data to evaluate the validity of the FDR approach. We tested a CAD phenotype inclusive of angina (SOFT; n(cases) = 10,801) as well as a stricter definition without angina (HARD; n(cases) = 6,482) and selected cases with the former phenotype to conduct a meta-analysis using the two most recent CAD GWAS(2,3). This approach identified 13 new loci at genome-wide significance, 12 of which were on our previous list of loci meeting the 5% FDR threshold(2), thus providing strong support that the remaining loci identified by FDR represent genuine signals. The 304 independent variants associated at 5% FDR in this study explain 21.2% of CAD heritability and identify 243 loci that implicate pathways in blood vessel morphogenesis as well as lipid metabolism, nitric oxide signaling and inflammation.

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Title: Association analyses based on false discovery rate implicate new loci for coronary artery disease
Creators - without role: Christopher P. Nelson - University of Leicester
Anuj Goel - University of Oxford
Adam S. Butterworth - University of Oxford
Stavroula Kanoni - Queen Mary University of London
Tom R. Webb - University of Leicester
Eirini Marouli - Queen Mary University of London
Lingyao Zeng - Clin Tech Univ Munchen, German Heart Ctr Munich, Partner Site Munich Heart Alliance, Munich, Germany
Ioanna Ntalla - Queen Mary University of London
Florence Y. Lai - University of Leicester
Jemma C. Hopewell - University of Oxford
Olga Giannakopoulou - Queen Mary University of London
Tao Jiang - University of Cambridge
Stephen E. Hamby - University of Leicester
Emanuele Di Angelantonio - University of Cambridge
Themistocles L. Assimes - Stanford University
Erwin P. Bottinger - Supreme Council Of Health
John C. Chambers - Imperial Coll London, Dept Epidemiol & Biostatist, London, England
Robert Clarke - University of Oxford
Colin N. A. Palmer - University of Dundee
Richard M. Cubbon - University of Leeds
Patrick Ellinor - Broad Institute
Raili Ermel - Tartu Univ Hosp, Dept Cardiac Surg, Tartu, Estonia
Evangelos Evangelou - Imperial Coll London, Dept Epidemiol & Biostatist, London, England
Paul W. Franks - Lund University
Christopher Grace - University of Oxford
Dongfeng Gu - College Station Medical Center
Aroon D. Hingorani - UCL, Inst Cardiovasc Sci, London, England
Joanna M. M. Howson - University of Cambridge
Erik Ingelsson - Stanford University
Adnan Kastrati - Clin Tech Univ Munchen, German Heart Ctr Munich, Partner Site Munich Heart Alliance, Munich, Germany
Thorsten Kessler - Clin Tech Univ Munchen, German Heart Ctr Munich, Partner Site Munich Heart Alliance, Munich, Germany
Theodosios Kyriakou - University of Oxford
Terho Lehtimaki - University of Tampere
Xiangfeng Lu - Stanford University
Yingchang Lu - Supreme Council Of Health
Winfried Maerz - University of Graz
Ruth McPherson - University of Ottawa
Andres Metspalu - University of Tartu
Mar Pujades-Rodriguez - University of Leeds
Arno Ruusalepp - Tartu Univ Hosp, Dept Cardiac Surg, Tartu, Estonia
Eric E. Schadt - Supreme Council Of Health
Amand F. Schmidt - UCL, Inst Cardiovasc Sci, London, England
Michael J. Sweeting - University of Cambridge
Pierre A. Zalloua - Supreme Council Of Health
Kamal AlGhalayini - King Abdulaziz University
Bernard D. Keavney - University of Manchester
Jaspal S. Kooner - London North West Healthcare NHS Trust
Ruth J. F. Loos - Supreme Council Of Health
Riyaz S. Patel - Farr Institute
Martin K. Rutter - University of Manchester
Maciej Tomaszewski - Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England
Ioanna Tzoulaki - Imperial Coll London, Dept Epidemiol & Biostatist, London, England
Eleftheria Zeggini - Wellcome Sanger Institute
Jeanette Erdmann - University of Lübeck
George Dedoussis - Harokopio University of Athens
Johan L. M. Bjorkegren - Gene
Heribert Schunkert - Clin Tech Univ Munchen, German Heart Ctr Munich, Partner Site Munich Heart Alliance, Munich, Germany
Martin Farrall - University of Oxford
John Danesh - University of Cambridge
Nilesh J. Samani - University of Leicester
Hugh Watkins - University of Oxford
Panos Deloukas - Queen Mary University of London
Uk Biobank CardioMetab
Publication Details: Nature genetics, Vol.49(9), pp.1385-1391
Publisher: Springer Nature
Number of pages: 9
Grant note: Tampere Tuberculosis Foundation Foundation Strategic Research NF-SI-0611-10170; CL-2011-11-003; NF-SI-0512-10165; NF-SI-0515-10091 / National Institute for Health Research; National Institutes of Health Research (NIHR) Tampere University Foundation LSHM-CT-2007-037273 / EU-FP6; European Commission FS/14/55/30806; SP/04/002; PG/16/49/32176; FS/12/80/29821; SP/09/002 / BHF; British Heart Foundation G51 / Action on Hearing Loss Heart AMP; Stroke Foundation of Canada; Heart & Stroke Foundation of Canada Emil Aaltonen Foundation EPIC-CVD Coordinating Centre team Wissenschaftsoffensive TMO Biogen 201668 / EU-FP7 (AtheroRemo) Pfizer Heart-Lung Foundation; Swedish Heart-Lung Foundation Medical Research Council (MRC); UK Research & Innovation (UKRI); Medical Research Council UK (MRC) Swedish Research Council (Distinguished Young Researchers Award); Swedish Research Council Yrjo Jahnsson Foundation Signe and Ane Gyllenberg Foundation 268834 / European Research Council (ERC); European Commission; Spanish Government PG/12/32/29544; RG/15/12/31616; RG/10/12/28456; RG/08/014/24067; FS/12/80/29821; FS/14/76/30933; RG/14/5/30893 / British Heart Foundation NNF15CC0018486 / TriPartite Immunometabolism Consortium-Novo Nordisk Foundation; Novo Nordisk Foundation HEALTH-F2-2013-601456 / FP7 279143 / EU-FP7 (EpiMigrant) NIHR-BRC Cambridge Wellcome Trust 560283 / Stockholm County Council University of Cambridge 01ZX1313A-K / German Ministry for Education and Research; Federal Ministry of Education & Research (BMBF) Canada Foundation for Innovation; CGIAR; Spanish Government G0601966; G0700931; G0800270 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) 12CVD02 / Transatlantic Networks of Excellence Award from the Leducq Foundation Andrea and Charles Bronfman Philanthropies Finnish Foundation of Cardiovascular Research CoG-2015_681742_NASCENT / European Commission; European Commission Joint Research Centre Novo Nordisk Foundation; Novocure Limited 268834 / ERC; European Research Council (ERC); European Commission MR/N011775/1; G0601966; G0800270; MR/L003120/1; G0700931 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) Sonderforschungsbereich CRC 1123 (B02) / Deutsche Forschungsgemeinschaft Centre of Research Excellence; German Research Foundation (DFG) RG/14/5/30893; FS/14/66/31293 / British Heart Foundation (BHF); British Heart Foundation Diabetes Research Foundation of the Finnish Diabetes Association UK National Institute for Health Research (NIHR); National Institutes of Health Research (NIHR) Karolinska Institutet Knut and Alice Wallenberg Foundation; Knut & Alice Wallenberg Foundation Canadian Institutes of Health Research; Canadian Institutes of Health Research (CIHR) AstraZeneca Roche Vitamins, Ltd. Torsten and Ragnar Soderberg Foundation BHF; British Heart Foundation Estonian Research Council Swedish Heart-Lung Foundation HEALTH-F2-2013-601456; 201668; 305739; HEALTH-F2-2012-279233 / EU-FP7; European Commission Merck; Merck & Company European Regional Development Fund (ERDF); European Commission Swedish Research Council; Swedish Research Council for Health Working Life & Welfare (Forte); Swedish Research Council Formas Pirkanmaa Regional Fund of the Finnish Cultural Foundation MR/L003120/1; G0800270; MC_qA137853; G0601966; G0700931 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) 090532/Z/09/Z; 084723/Z/08/Z; 098051 / Wellcome Trust NIHR-BRC Imperial College Healthcare NHS Trust NIHR; National Institutes of Health Research (NIHR) Merck and Co; Merck & Company RP-PG-0407-10371 / NIHR; National Institutes of Health Research (NIHR) 9M048; 9N035 / Tampere University Hospital Medical Funds NNF15SA0018486 / Novo Nordisk Fonden; Novo Nordisk Foundation
Identifiers: 9934319708331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article