Abstract 18346: Common Genetic Variants and Subclinical Atherosclerosis in the Multi-Ethnic Study of Atherosclerosis
Introduction: Subclinical atherosclerosis (sCVD), measured by coronary artery calcium (CAC), carotid intima media thickness (CIMT) and carotid plaque (CP), has been associated with cardiovascular disease (CVD). Genome Wide Association Studies (GWAS) of CVD have focused on Caucasian populations.
Hypothesis: This study tested the hypothesis that these associations would differ in populations from distinct genetic backgrounds.
Methods: The associations between sCVD and 42 single nucleotide polymorphisms (SNPs) from published GWAS of sCVD and CVD were tested in 8224 Multi-Ethnic Study of Atherosclerosis (MESA) participants and MESA Family participants (2685 Caucasians (EUA), 777 Chinese (CHN), 2588 African Americans (AFA), and 2174 Hispanic (HIS)). An additive model was adjusted for SNPs, age, gender, site of ascertainment, principal components, and CVD risk factors, with SNP significance defined by a Bonferroni-corrected p<0.001. Relatedness was accounted for by a linear mixed-effects model for quantitative traits or generalized estimating equations for binary traits.
Results: The 9p21 region (rs1333049 and rs4977574) was associated with CAC in EUA (p=5E-6 and 1E-5), and in HIS (p=2E-4 and 1E-4), same direction of association to EUA) but not in AFA or CHN. In CHN, rs1878406 (EDNRA) associated with CIMT (p=6E-4). In HIS, rs964184 (APOA5) associated with CAC (p=2E-5). Meta-analysis across the four ethnic/racial groups confirmed the association between the 9p21 SNPs and CAC (p=2E-9 and 3E-11) (heterogeneity p-values of 0.09 and 0.4) and showed associations between rs216172 (SMG6) and CIMT and rs1994016 (ADAMTS7) and CAC (p=1E-4 for both). Of the 42 SNPs tested, only rs1333049 and rs4977574 replicated in EUA. There were no significant associations in AFA. A smaller sample size limited power in CHN.
Conclusion: In non-Caucasians in MESA, associations were found with SNPs previously identified in EUA GWAS for CVD and sCVD, but not in all loci, suggesting novel variants and/or pathways in risk of CVD in minority populations.
- © 2013 by American Heart Association, Inc.