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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-09

AUTHORS

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 N A Palmer, Richard M Cubbon, Patrick Ellinor, Raili Ermel, Evangelos Evangelou, 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-Rodriguez, Arno Ruusalepp, Eric E Schadt, Amand F Schmidt, Michael J Sweeting, Pierre A Zalloua, Kamal AlGhalayini, Bernard D Keavney, Jaspal S Kooner, Ruth J F Loos, Riyaz S Patel, Martin K Rutter, Maciej Tomaszewski, Ioanna Tzoulaki, Eleftheria Zeggini, Jeanette Erdmann, George Dedoussis, Johan L M Björkegren, EPIC-CVD Consortium, CARDIoGRAMplusC4D, Biobank CardioMetabolic Consortium CHD working group, Heribert Schunkert, Martin Farrall, John Danesh, Nilesh J Samani, Hugh Watkins, Panos Deloukas

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. More... »

PAGES

1385-1391

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.3913

    DOI

    http://dx.doi.org/10.1038/ng.3913

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1090747969

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/28714975


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