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.