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

    Nature genetics, 09/2017, Volume: 49, Issue: 9
    Journal Article

    Genome-wide association studies (GWAS) in coronary artery disease (CAD) had identified 66 loci at 'genome-wide significance' (P < 5 × 10 ) 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 = 10,801) as well as a stricter definition without angina (HARD; n = 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.

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