| Literature DB >> 28714975 |
Christopher P Nelson1,2, Anuj Goel3,4, Adam S Butterworth5,6, Stavroula Kanoni7,8, Tom R Webb1,2, Eirini Marouli7,8, Lingyao Zeng9, Ioanna Ntalla7,8, Florence Y Lai1,2, Jemma C Hopewell10, Olga Giannakopoulou7,8, Tao Jiang5, Stephen E Hamby1,2, Emanuele Di Angelantonio5,6, Themistocles L Assimes11, Erwin P Bottinger12, John C Chambers13,14,15, Robert Clarke10, Colin N A Palmer16,17, Richard M Cubbon18, Patrick Ellinor19, Raili Ermel20, Evangelos Evangelou13,21, Paul W Franks22,23,24, Christopher Grace3,4, Dongfeng Gu25, Aroon D Hingorani26, Joanna M M Howson5, Erik Ingelsson27, Adnan Kastrati9, Thorsten Kessler9, Theodosios Kyriakou3,4, Terho Lehtimäki28, Xiangfeng Lu27, Yingchang Lu12,29, Winfried März30,31,32, Ruth McPherson33, Andres Metspalu34, Mar Pujades-Rodriguez35, Arno Ruusalepp20,36, Eric E Schadt37, Amand F Schmidt26, Michael J Sweeting5, Pierre A Zalloua38,39, Kamal AlGhalayini40, Bernard D Keavney41,42, Jaspal S Kooner14,15,43, Ruth J F Loos12,44, Riyaz S Patel45,46, Martin K Rutter47,48, Maciej Tomaszewski42,49, Ioanna Tzoulaki13,21, Eleftheria Zeggini50, Jeanette Erdmann51,52,53, George Dedoussis54, Johan L M Björkegren36,37,55, Heribert Schunkert9, Martin Farrall3,4, John Danesh5,6,56, Nilesh J Samani1,2, Hugh Watkins3,4, Panos Deloukas7,8,57.
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; 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.Entities:
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Year: 2017 PMID： 28714975 DOI： 10.1038/ng.3913
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330