Common genetic variation in circadian clock genes are associated with cardiovascular risk factors in an African American and Hispanic/Latino cohort.

Abstract

Misalignment of the internal circadian time with external physical time due to environmental factors or due to genetic variantion in circadian clock genes has been associated with increased incidence of cardiovascular risk factors. Common genetic variation in circadian genes in the United States have been identified predominantly in European ancestry individuals. We therefore examined the association between circadian clock single nucleotide polymorphisms (SNPs) in Clock, Cry1, Cry2, Bmal1 and Per3 genes and cardiovascular risk factors in African Americans and Hispanic/Latinos. We analyzed 17 candidate circadian SNPs in 1,166 subjects who self-identified as African-American or Hispanic/Latino and were enrolled in the UIC Cohort of Patients, Family and Friends. We found significant differences in the minor allele frequencies between African American and Hispanic/Latino subjects. Our analyses also established ethnic-specific SNPs that are associated with cardiovascular risk factors. In Hispanic/Latinos, the rs6850524 in Clock was associated with increased risk for hypertension, meanwhile rs12649507, rs4864546, and rs4864548 reduced the risk, also rs8192440 (Cry1) reduced the risk for type 2 diabetes. In African Americans, the Clock rs1801260 and rs6850524 were negatively associated with the presence of obesity; Bmal1 rs11022775 reduced the risk for dyslipidemia; and the Cry2 rs2292912 increased the risk for dyslipidemia and diabetes. Genetic variations in candidate circadian-clock genes are associated with risk factors for cardiovascular disease in African-Americans and Hispanic/Latinos. Our findings may help to improve cardiovascular risk assessment as well as better understand how circadian misalignment impacts cardiovascular risk in diverse populations.