Abstract MP55: Genetic Loci Associated with Ideal Cardiovascular Health: A Meta-Analysis of Genome-wide Association Studies
Background: Genetic loci have been associated with individual cardiovascular risk factors; however little is known about potential genes which may be involved in overall cardiovascular (CV) health. Ideal CV health is associated with lower CVD risk and has been shown to be heritable, but it is unknown whether there are potential common underlying genes.
Objective: To carry out a genome-wide association study (GWAS) to investigate genetic determinants of ideal CV health.
Methods: We examined two dichotomous phenotypes of ideal health - Clinical (untreated cholesterol < 200 mg/dl; untreated blood pressure (BP) <120/<80; not diabetic) and Clinical+Behavioral (untreated cholesterol < 200 mg/dl; untreated BP <120/<80; not diabetic; not a current smoker; BMI <25 kg/m2) among Caucasian participants aged 50 ± 5 years at the time of exam. In this discovery phase, we performed meta-analysis of 4 GWAS (n=13,599) from MESA, CARDIA, ARIC and Framingham cohorts. The prevalence across studies ranged from 10-30% for Clinical and 5-13% for Clinical+Behavioral ideal health. Each study conducted logistic regression analyses using an additive SNP model for each phenotype. Models were adjusted for age, sex, site and principal components of ancestry. Study-specific results were combined using inverse-variance weighted meta-analysis implemented in METAL.
Results: We identified a SNP (rs445925) in the APOC1, APOE region that was associated with Clinical ideal health at a genome-wide level of significance (p<3.6x10-10, OR 1.79). These results were consistent across cohorts; however, the imputation quality of the SNP averaged 0.3 and there were no other significant associations in this region. The minor allele frequency for this SNP was 0.14.
Conclusion: Our findings suggest a common SNP in the APOC1/APOE region, which encodes Apolipoprotein C1 and is associated with cholesterol levels and metabolism, may be associated with ideal health. This SNP has been identified in previous GWAS of IMT and LDL levels. Replication of these findings is needed.
- © 2013 by American Heart Association, Inc.