Admixture mapping of coronary artery calcification in African Americans from the NHLBI family heart study

Abstract

Background: Coronary artery calcification (CAC) is an imaging biomarker of coronary atherosclerosis. In European Americans, genome-wide association studies (GWAS) have identified several regions associated with coronary artery disease. However, few large studies have been conducted in African Americans. The largest meta-analysis of CAC in African Americans failed to identify genome-wide significant variants despite being powered to detect effects comparable to effects identified in European Americans. Because CAC is different in prevalence and severity in African Americans and European Americans, admixture mapping is a useful approach to identify loci missed by GWAS. Results: We applied admixture mapping to the African American cohort of the Family Heart Study and identified one genome-wide significant region on chromosome 12 and three potential regions on chromosomes 6, 15, and 19 that are associated with CAC. Follow-up studies using previously reported GWAS meta-analysis data suggest that the regions identified on chromosome 6 and 15 contain variants that are possibly associated with CAC. The associated region on chromosome 6 contains the gene for BMP-6, which is expressed in vascular calcific lesions. Conclusions: Our results suggest that admixture mapping can be a useful hypothesis-generating tool to identify genomic regions that contribute to complex diseases in genetically admixed populations.