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

Genome-wide association studies (GWAS) in coronary artery disease (CAD) have identified 66 loci at ‘genome-wide significance’ (p < 5 × 10-8) but a much larger number of putative loci at a false discovery rate (FDR) of 5%1-4. 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 it (HARD; Ncases=6,482) and selected the former for conducting a meta-analysis with the two most recent CAD GWASs2-3. This approach identified 13 new loci at genome-wide significance, 12 of which were in our previous 5% FDR list2, and provided strong support that the remaining FDR loci represent genuine signals. The set of 304 independent variants at 5% FDR in this study explain 21.2% of CAD heritability and identified 243 loci that implicate pathways in blood vessel morphogenesis as well as lipid metabolism, nitric oxide signaling and inflammation.