Admixture mapping for hypertension loci with genome-scan markers

Abstract

Identification of genetic variants that contribute to risk of hypertension is challenging. As a complement to linkage and candidate gene association studies, we carried out admixture mapping using genome-scan microsatellite markers among the African American participants in the US National Heart, Lung, and Blood Institute's Family Blood Pressure Program. This population was assumed to have experienced recent admixture from ancestral groups originating in Africa and Europe. We used a set of unrelated individuals from Nigeria to represent the African ancestral population and used the European Americans in the Family Blood Pressure Program to provide estimates of allele frequencies for the European ancestors. We genotyped a common set of 269 microsatellite markers in the three groups at the same laboratory. The distribution of marker location-specific African ancestry, based on multipoint analysis, was shifted upward in hypertensive cases versus normotensive controls, consistent with linkage to genes conferring susceptibility. This shift was largely due to a small number of loci, including five adjacent markers on chromosome 6q and two on chromosome 21q. These results suggest that chromosome 6q24 and 21q21 may contain genes influencing risk of hypertension in African Americans.

Relationship between hypertension and admixture in post-menopausal African American and Hispanic American women

“…[2][3][4] Previous studies have also suggested that AFR admixture in AFA was associated with hypertension but either failed to reach statistical significance or showed only a modest effect. [6][7][8] This study shows statistically significant association of AFR admixture and hypertension in both AFA and HA population groups. Our study differs from previous studies with respect to having a much larger sample size and that our participants were restricted to adult post-menopausal women.…”

“…[2][3][4] A potential contributing factor to the differences in prevalence of hypertension may be the degree of admixture within individuals residing in the United States, a highly heterogeneous genetic population. Previous studies have either not shown a statistically significant difference in African admixture within AFA subjects with and without hypertension 6,7 or have shown modest differences. 8 Although one group found hypertension association with specific African inherited chromosomal regions 6 these findings have not been supported by other studies.…”

“…Previous studies have either not shown a statistically significant difference in African admixture within AFA subjects with and without hypertension 6,7 or have shown modest differences. 8 Although one group found hypertension association with specific African inherited chromosomal regions 6 these findings have not been supported by other studies. 7 In addition, these previous studies did not consider socioeconomic status (SES) as a possible confounder.…”

Admixture as the basis for genetic mapping

“…Measures of excess admixture form the basis for mapping phenotypic variation and loci that contribute to isolation between taxa [4,28], although different implementations of admixture mapping parameterize and utilize excess admixture in different ways. http://doc.rero.ch 2 mapping incorporates population structure through its measure of excess ancestry (Box 1).…”

“…http://doc.rero.ch [27][28][29][30][31]. However, multiple studies have identified genetic variants associated with lighter and darker skin pigmentation in humans [32][33][34], a trait that might be differentially selected in regions with low and high ultraviolet radiation (UVR), owing to known associations between skin pigmentation and vitamin D synthesis and protection from UVR [34,35].…”