Association analyses based on false discovery rate implicate new loci for coronary artery disease21 Aug 2017
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; ncases = 10,801) as well as a stricter definition without angina (HARD; ncases = 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.
|Authors:||Nelson, CP, Goel, A, Butterworth, Adam, Kanoni, S, Webb, TR, Marouli, E, Zeng, L, Ntalla, I, Lai, FY, Hopewell, JC, Giannakopoulou, O, Jiang, Tao, Hamby, SE, Di Angelantonio, Emanuele, Assimes, TL, Bottinger, EP, Chambers, JC, Clarke, R, Palmer, CNA, Cubbon, RM, Ellinor, P, Ermel, R, Evangelou, E, Franks, PW, Grace, C, Gu, D, Hingorani, AD, Howson, Joanna, Ingelsson, E, Kastrati, A, Kessler, T, Kyriakou, T, Lehtimäki, T, Lu, X, Lu, Y, März, W, McPherson, R, Metspalu, A, Pujades-Rodriguez, M, Ruusalepp, A, Schadt, EE, Schmidt, AF, Sweeting, Michael, Zalloua, PA, AlGhalayini, K, Keavney, BD, Kooner, JS, Loos, RJF, Patel, RS, Rutter, MK, Tomaszewski, M, Tzoulaki, I, Zeggini, E, Erdmann, J, Dedoussis, G, Björkegren, JLM, EPIC-CVD Consortium, CARDIoGRAMplusC4D, UK Biobank CardioMetabolic Consortium CHD working group, Schunkert, H, Farrall, M, Danesh, John, Samani, NJ, Watkins, H, Deloukas, P|
|Institution:||University of Cambridge|
|Keywords:||cardiovascular diseases, genetics, genome-wide association studies, sequence annotation|