Abstract MP35: Association of Genetic Variants with Incident Coronary Heart Disease in African Americans
Introduction: Coronary heart disease (CHD) is a leading cause of morbidity and mortality in the U.S., and disproportionally affects African Americans. Given the evidence for genetic susceptibility to CHD in African Americans and lagging discovery efforts in this population, we propose to search for gene variants that contribute to incident CHD risk in African Americans.
Methods: We examined the evidence for association of genome wide genetic markers with incident CHD using the high density custom array MetaboChip using data from two U.S. cohort studies comprising 7,967 African American individuals (Women’s Health Initiative and the Atherosclerosis Risk in Communities). Genome-wide ancestry estimates (principal components) were determined using Eigensoft. We used Cox proportional hazard models, adjusted for age and population stratification. Study- and sex-stratified results were combined using fixed effect meta-analysis. A Bonferroni corrected P< 2.8 x 10-7 was considered a significant array wide finding, and a P<2.0 x 10-3 was considered replication for index or proxy for the 24 CHD loci represented in the array.
Results: Mean age varied from 53 to 61 years. After excluding prevalent CHD, there were 581 incident CHD events. We identified two novel loci significantly associated with incident CHD including an intergenic variant nearby ADRA1A (allele frequency=0.52). Of previously published CHD loci, the best evidence for association was at SORT1, where rs583104 (minor allele frequency [MAF] 0.27, P = 3.9x10–4) is in complete linkage disequilibrium (LD) with rs599839, the SNP described in individuals of European ancestry. Other CHD loci with SNPs associated with CHD were PPAP2B (rs17114018, MAF 0.12, P=1.0 x 10-3), CXCL12 (rs880174, MAF 0.05, P=3.0 x 10-4), and PCSK9 (rs2317949, MAF= 0.28, P=2.8 x 10–3). These SNPs were in low LD with the SNPs reported in genome wide association case-control studies in individuals of European ancestry.
Conclusions: We identified two potential novel loci for incident CHD in African Americans and replicated a variant association in SORT1 from case-control studies of European ancestry. Replication in additional African American and European samples is currently underway. Our findings suggest that studies of African ancestry individuals may contribute to characterization of the genetic architecture of CHD traits.
- © 2013 by American Heart Association, Inc.