A comprehensive 1,000 Genomes-based genome-wide association meta-analysis of coronary artery disease.
Nikpay M, Goel A, Won HH et al.
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Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of ∼185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 million low-frequency (0.005 < MAF < 0.05) variants. In addition to confirming most known CAD-associated loci, we identified ten new loci (eight additive and two recessive) that contain candidate causal genes newly implicating biological processes in vessel walls. We observed intralocus 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.
42,096 European ancestry cases, 361 African American cases, 758 Hispanic American cases, 12,658 South Asian ancestry cases, 1,802 Lebanese ancestry cases, 3,614 East Asian ancestry cases, 99,121 European ancestry controls, 2,778 African American controls, 3,337 Hispanic American controls, 12,899 South Asian ancestry controls, 466 Lebanese ancestry controls, 7,709 East Asian ancestry controls
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