Association analyses based on false discovery rate implicate new loci for coronary artery disease

• Verfasst von: Nelson, Christopher P. [VerfasserIn]
• Verfasst von: März, Winfried [VerfasserIn]
• Titel: Association analyses based on false discovery rate implicate new loci for coronary artery disease
• Verf.angabe: 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 NA Palmer, Richard M Cubbon, Patrick Ellinor, Raili Ermel, Evangelos Evangelou, Paul W Franks, Christopher Grace, Dongfeng Gu, Aroon D Hingorani, Joanna MM 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 JF Loos, Riyaz S Patel, Martin K Rutter, Maciej Tomaszewski, Ioanna Tzoulaki, Eleftheria Zeggini, Jeanette Erdmann, George Dedoussis, Johan LM Björkegren, Epic-Cvd Consortium, CARDIoGRAMplusC4D, The UK Biobank CardioMetabolic Consortium CHD working Group, Heribert Schunkert, Martin Farrall, John Danesh, Nilesh J Samani, Hugh Watkins and Panos Deloukas
• E-Jahr: 2017
• Jahr: 17 July 2017
• Umfang: 7 S.
• Fussnoten: Gesehen am 27.08.2018
• Titel Quelle: Enthalten in: Nature genetics
• Ort Quelle: London : Macmillan Publishers Limited, part of Springer Nature, 1992
• Jahr Quelle: 2017
• Band/Heft Quelle: 49(2017), 9, Seite 1385-1391
• ISSN Quelle: 1546-1718
• DOI: doi:10.1038/ng.3913
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1580399606

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 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.