Genome-wide association studies have identified 11 common variants convincingly associated with coronary artery disease (CAD)¹⁻⁷, a modest number considering the apparent heritability of CAD⁸. All of these variants have been discovered in European populations. We report a meta-analysis of four large genome-wide association studies of CAD, with ∼575,000 genotyped SNPs in a discovery dataset comprising 15,420 individuals with CAD (cases) (8,424 Europeans and 6,996 South Asians) and 15,062 controls. There was little evidence for ancestry-specific associations, supporting the use of combined analyses. Replication in an independent sample of 21,408 cases and 19,185 controls identified five loci newly associated with CAD (P < 5 × 10⁻⁸ in the combined discovery and replication analysis): LIPA on 10q23, PDGFD on 11q22, ADAMTS7-MORF4L1 on 15q25, a gene rich locus on 7q22 and KIAA1462 on 10p11. The CAD-associated SNP in the PDGFD locus showed tissue-specific cis expression quantitative trait locus effects. These findings implicate new pathways for CAD susceptibility.
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ADAM Proteins, ADAMTS7 Protein, Adult, Aged, Asian Continental Ancestry Group, Case-Control Studies, Coronary Artery Disease, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Lymphokines, Male, Middle Aged, Oligonucleotide Array Sequence Analysis, Platelet-Derived Growth Factor, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Sterol Esterase, Transcription Factors