Title |
Association analyses based on false discovery rate implicate new loci for coronary artery disease
|
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Published in |
Nature Genetics, July 2017
|
DOI | 10.1038/ng.3913 |
Pubmed ID | |
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, 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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 14 | 34% |
United Kingdom | 5 | 12% |
Australia | 3 | 7% |
Netherlands | 1 | 2% |
Argentina | 1 | 2% |
Denmark | 1 | 2% |
Canada | 1 | 2% |
Unknown | 15 | 37% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 21 | 51% |
Scientists | 20 | 49% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 379 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 84 | 22% |
Researcher | 64 | 17% |
Student > Master | 36 | 9% |
Student > Doctoral Student | 25 | 7% |
Student > Bachelor | 21 | 6% |
Other | 67 | 18% |
Unknown | 82 | 22% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 83 | 22% |
Medicine and Dentistry | 76 | 20% |
Agricultural and Biological Sciences | 49 | 13% |
Nursing and Health Professions | 14 | 4% |
Computer Science | 8 | 2% |
Other | 55 | 15% |
Unknown | 94 | 25% |