作者
Christopher P. Nelson,Anuj Goel,Adam S. Butterworth,Stavroula Kanoni,Tom R. Webb,Eirini Marouli,Lingyao Zeng,Ιωάννα Ντάλλα,Florence Lai,Jemma C. Hopewell,Olga Giannakopoulou,Tao Jiang,Stephen E. Hamby,Emanuele Di Angelantonio,Themistocles L. Assimes,Erwin P. Böttinger,John C. Chambers,Robert Clarke,Colin N. A. Palmer,Richard M. Cubbon,Patrick T. Ellinor,Raili Ermel,Εvangelos Εvangelou,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‐Rodríguez,Arno Ruusalepp,Eric E. Schadt,Amand F. Schmidt,Michael Sweeting,Pierre Zalloua,Kamal Alghalayini,Bernard Keavney,Jaspal S. Kooner,Ruth J. F. Loos,Riyaz Patel,Martin K. Rutter,Maciej Tomaszewski,Ioanna Tzoulaki,Eleftheria Zeggini,Jeanette Erdmann,George Dedoussis,Johan Björkegren,Heribert Schunkert,Martin Farrall,John Danesh,Nilesh J. Samani,Hugh Watkins,Panos Deloukas
摘要
Hugh Watkins and colleagues meta-analyze data from the UK Biobank along with recent genome-wide association studies for coronary artery disease. They identify 13 new loci that were genome-wide significant and 243 loci at a 5% false discovery rate. 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 GWAS2,3. This approach identified 13 new loci at genome-wide significance, 12 of which were on our previous list of loci meeting the 5% FDR threshold2, 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.