Large-scale association analysis identifies new risk loci for coronary artery disease

Coronary artery disease ( CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CADcases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CADto 46, and a further 104 independent variants (r(2) < 0.2) strongly associated with CADat a 5% false discovery rate(FDR). Together, these variants explain approximately 10.6% of CADheritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networkscomprising 85% of these putative genesinvolved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CADand identifies key biological pathways.