Genome‐wide admixture mapping for coronary artery calcification in African Americans: the NHLBI Family Heart Study

Abstract

Coronary artery calcification (CAC) is an important measure of subclinical coronary atherosclerosis and an independent predictor of coronary heart disease. To identify the genetic loci contributing to CAC, we conducted a genome-wide scan with 374 microsatellite markers by applying admixture mapping to 618 African American participants in the US National Heart, Lung, and Blood Institute Family Heart Study, in which 868 European American participants from family heart study and 157 Africans genotyped by the Marshfield Medical Genetics Center were used as the two reference founding populations for the African Americans, and a computer program based on a Markov Chain Monte Carlo algorithm, STRUCTURE 2.1, was used to estimate European and African ancestries among African Americans. A permutation test for random repeated sampling regression of CAC score on marker specific African ancestry found 22 markers statistically significant at the 0.05 level and four markers, D10S189 at 10p14, D20S159 at 20q13, D12S1294 at 12q14, and D6S1053 at 6q12, significant at the 0.01 level. D10S189 and D6S1053 were further confirmed at the 0.05 significance level by regression of CAC on allelic copy number, in which individual ancestry was used as a genetic background covariate to control possible stratification in African Americans. On the basis of the results from this and other independent studies, the location of D6S1053 at 80cM on chromosome 6 (6q12) seems to harbor a highly promising quantitative trait loci for atherosclerosis.

Whole Brain and Regional Hyperintense White Matter Volume and Blood Pressure

“…The linkage results for the subcortical HWM volume only reached suggesting significance, but the highest LOD score (LOD=2.68) was observed for the bivariate analysis with the SBP. This region, 10q24–q26, has been identified as a region of a significant linkage by univariate analyses of several atherosclerosis traits 28 , therefore supporting the hypothesis of a small-vessel mediated origin of subcortical HWM. We did not interpret the lack of the statistically significant linkage between subcortical HWM volume and SBP as an indication that hypertension does not play a role in the formation of the subcortical HWM lesions.…”

Genetics in Arterial Calcification

“…The marker D10S189 at map position 19.0 cM on chromosome 10p14 gave the strongest signal ( P =0.0012); candidate genes within this region include CALML5 (calmodulin-like 5) and CALML3 (calmodulin-like 3), which encode calcium-binding proteins. 17 …”

African ancestry is associated with risk of asthma and high total serum IgE in a population from the Caribbean Coast of Colombia

“…Substantial advances in the identiWcation of risk variants associated with complex traits for which a greater proportion of minority populations suVer from the disease of interest have been elucidated using admixture mapping. They include cardiovascular disease (Zhang et al 2008;Zhu et al 2005), multiple sclerosis , prostate cancer (Freedman et al 2006), and serum IL-6 levels ) and asthma . Several characteristics of this dataset facilitate the design of admixture mapping analysis, including the signiWcant association between African ancestry and asthma and total IgE levels and the wide distributions of the individual admixture proportions.…”