Abstract 15437: Replication of the Association of PSRC1 and MTHFD1L with Coronary Artery Disease: the Multi-Ethnic Study of Atherosclerosis
Introduction GWAS have identified thirty single nucleotide polymorphisms (SNPs) associated with coronary heart disease (CHD); however the majority of these analyses are in subjects of Caucasian ancestry. We analyzed these previously reported SNPs associated with CHD events within four separate ethnic groups in the Multi-Ethnic Study of Atherosclerosis (MESA). Associations were validated in the Health Aging and Body Composition (Health ABC) cohort.
Methods Cox proportional hazards model assuming an additive genetic effect adjusting for age, gender, study site, and genetic ancestral principal components was performed on 2,528 Caucasians, 1,673 African Americans, 1,449 Hispanics, and 775 Chinese subjects with 263 total events. SNPs with a nominal statistical significance of 0.05 in Caucasians and African Americans were further validated using the Health, Aging and Body Composition (Health ABC) cohort (2,800 subjects; 1661 Caucasians and 1139 African Americans with 954 total events).
Results Among the three SNPs within the Caucasian group with nominal significance, rs599839 of the PSRC1 gene on chromosome 1 with a p value of 0.01 replicated within the Health ABC Caucasian cohort. Among the five SNPs within the African American group with nominal significance, rs6922269 of the MTHFD1L gene on chromosome 6 with a p value of 0.03 replicated within the Health ABC African American cohort [Table 1].
Conclusion Two of the 30 previously published SNP associations with coronary artery disease, rs599839 within the PSRC1 gene on chromosome 1 and rs6922269 within the MTHFD1L gene on chromosome 6, revealed nominal significance in the MESA cohort and these findings were replicated within the Health ABC cohort. Together these data from two large independent cohorts provide further support for an association of these SNPs with CHD and justify additional research into the possible pathophysiologic roles of these genes, or genes within linkage disequilibrium to these SNPs.
- © 2011 by American Heart Association, Inc.