Abstract 17979: A Genome-Wide Association Study of Risk of Coronary Artery Disease in European and South Asian Populations
Background: Genome-wide association (GWAS) studies of coronary artery disease (CAD) have identified several common variants for CAD susceptibility, but these explain only a small fraction of the predicted genetic risk. Studies of cases of early onset CAD, those with positive family history, or of South Asian populations (that have considerably increased risk of CAD) may facilitate the detection of novel CAD susceptibility loci. We report on a prospective meta-analysis of four large unpublished GWAS studies of CAD with replication in independent populations.
Methods: The discovery stage involved a meta-analysis of data for over 500,000 SNPs in four case-control studies involving a total of 15,418 CAD cases (with average age of onset under 60 years) and 15,067 controls that were matched for ethnicity. Data were collected from two European populations (PROCARDIS [5720 genetically enriched cases] and the Heart Protection Study [2704 cases]) and two South Asian populations (PROMIS [4253 cases] and LOLIPOP [2741 cases]). After quality control exclusions, data for 574,911 SNPs with frequency ≥1% were entered into a fixed effects meta-analysis. Heterogeneity between studies and between ethnicities was assessed. The primary analyses examined the associations of SNPs with CAD in: (i) all four studies in combination; (ii) the two European Studies; and (iii) the two South Asian studies. Independent replication of 50 SNPs from 35 loci was tested in about 19,000 cases and 14,000 controls of predominantly European origin.
Results and Conclusions: The analysis confirmed genome-wide statistical significance for previously reported susceptibility loci (e.g. 9p21.3: p<10−28; 1p13.3: p<10−11). A number of novel associations of genome-wide significance were identified with small effect sizes consistent with CAD susceptibility being influenced by a large number of loci with modest effects. Although examples were identified where there were differences in allele frequency or effect size between Europeans and South Asians, there was little evidence to suggest clinically meaningful differences in genetic susceptibility to CAD between these ethnically diverse populations.
- © 2010 by American Heart Association, Inc.