Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely
based on genome-wide association studies (GWAS) analysis of common SNPs. Leveraging
phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of 185
thousand CAD cases and controls, interrogating 6.7 million common (MAF>0.05) as well as 2.7
million low frequency (0.005<MAF<0.05) variants. In addition to confirmation of most known
CAD loci, we identified 10 novel loci, eight additive and two recessive, that contain candidate
genes that newly implicate biological processes in vessel walls. We observed intra-locus allelic
heterogeneity but little evidence of low frequency variants with larger effects and no evidence of
synthetic association. Our analysis provides a comprehensive survey of the fine genetic
architecture of CAD showing that genetic susceptibility to this common disease is largely
determined by common SNPs of small effect size