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. CubbonPatrick 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 Lehtimäki, Xiangfeng Lu, Yingchang Lu, Winfried März, 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. Björkegren, Heribert Schunkert, Martin Farrall, John Danesh, Nilesh J. Samani, Hugh Watkins*, Panos Deloukas

*Korrespondierende/r Autor/-in für diese Arbeit
8 Zitate (Scopus)

Abstract

Genome-wide association studies (GWAS) in coronary artery disease (CAD) had identified 66 loci at 'genome-wide significance' (P < 5 × 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. 1,2,3,4). 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. 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, 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.
OriginalspracheEnglisch
ZeitschriftNature Genetics
Jahrgang49
Ausgabenummer9
Seiten (von - bis)1385-1391
Seitenumfang7
ISSN1061-4036
DOIs
PublikationsstatusVeröffentlicht - 01.09.2017

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