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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.

Original publication

DOI

10.1038/ng.3913

Type

Journal article

Journal

Nat Genet

Publication Date

09/2017

Volume

49

Pages

1385 - 1391

Keywords

Coronary Artery Disease, Genetic Association Studies, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Health Information Systems, Humans, Meta-Analysis as Topic, Phenotype, Polymorphism, Single Nucleotide, Reproducibility of Results, Risk Factors, United Kingdom