Association analyses based on false discovery rate implicate new loci for coronary artery disease.
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Abstract | Genome-wide association studies (GWAS) in coronary artery disease (CAD) had identified 66 loci at 'genome-wide significance' (P 5 × 10) 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; n = 10,801) as well as a stricter definition without angina (HARD; n = 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. |
Year of Publication | 2017
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Journal | Nat Genet
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Volume | 49
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Issue | 9
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Pages | 1385-1391
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Date Published | 2017 Sep
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ISSN | 1546-1718
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DOI | 10.1038/ng.3913
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PubMed ID | 28714975
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Grant list | G0800270 / Medical Research Council / United Kingdom
MC_QA137853 / Medical Research Council / United Kingdom
G0700931 / Medical Research Council / United Kingdom
RG/08/014/24067 / British Heart Foundation / United Kingdom
PG/12/32/29544 / British Heart Foundation / United Kingdom
MR/L003120/1 / Medical Research Council / United Kingdom
S10 OD018522 / OD / NIH HHS / United States
G0601966 / Medical Research Council / United Kingdom
RG/14/5/30893 / British Heart Foundation / United Kingdom
FS/12/80/29821 / British Heart Foundation / United Kingdom
FS/14/76/30933 / British Heart Foundation / United Kingdom
RG/10/12/28456 / British Heart Foundation / United Kingdom
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