Variants in CXADR and F2RL1 are associated with blood pressure and obesity in African-Americans in regions identified through admixture mapping

OBJECTIVE: Genetic variants in 296 genes in regions identified through admixture mapping of hypertension, BMI, and lipids were assessed for association with hypertension, blood pressure (BP), BMI, and high-density lipoprotein cholesterol (HDL-C). METHODS: This study identified coding SNPs identified from HapMap2 data that were located in genes on chromosomes 5, 6, 8, and 21, wherein ancestry association evidence for hypertension, BMI, or HDL-C was identified in previous admixture mapping studies. Genotyping was performed in 1733 unrelated African-Americans from the National Heart, Lung and Blood Institute's Family Blood Pressure Project, and gene-based association analyses were conducted for hypertension, SBP, DBP, BMI, and HDL-C. A gene score based on the number of minor alleles of each SNP in a gene was created and used for gene-based regression analyses, adjusting for age, age, sex, local marker ancestry, and BMI, as applicable. An individual's African ancestry estimated from 2507 ancestry-informative markers was also adjusted for to eliminate any confounding due to population stratification. RESULTS: CXADR (rs437470) on chromosome 21 was associated with SBP and DBP with or without adjusting for local ancestry (P < 0.0006). F2RL1 (rs631465) on chromosome 5 was associated with BMI (P = 0.0005). Local ancestry in these regions was associated with the respective traits as well. CONCLUSION: This study suggests that CXADR and F2RL1 likely play important roles in BP and obesity variation, respectively; and these findings are consistent with those of other studies, so replication and functional analyses are necessary.