Zhang Qunyuan, Lewis Cora E, Wagenknecht Lynne E, Myers Richard H, Pankow James S, Hunt Steven C, North Kari E, Hixson James E, Jeffrey Carr J, Shimmin Lawrence C, Borecki Ingrid, Province Michael A
Division of Statistical Genomics, Washington University School of Medicine, St. Louis, Missouri 63108, USA.
Genet Epidemiol. 2008 Apr;32(3):264-72. doi: 10.1002/gepi.20301.
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.
冠状动脉钙化（CAC）是亚临床冠状动脉粥样硬化的一项重要指标，也是冠心病的独立预测因子。为了确定导致CAC的基因位点，我们对美国国立心肺血液研究所家族心脏研究中的618名非裔美国人参与者进行了全基因组扫描，使用了374个微卫星标记，并应用混合映射法。在该研究中，来自家族心脏研究的868名欧裔美国人参与者以及由马什菲尔德医学遗传学中心进行基因分型的157名非洲人被用作非裔美国人的两个参考奠基人群。我们使用基于马尔可夫链蒙特卡罗算法的计算机程序STRUCTURE 2.1来估计非裔美国人中的欧洲和非洲血统。对CAC评分在标记特异性非洲血统上的随机重复抽样回归进行置换检验，发现22个标记在0.05水平上具有统计学意义，4个标记，即位于10p14的D10S189、位于20q13的D20S159、位于12q14的D12S1294和位于6q12的D6S1053，在0.01水平上具有统计学意义。通过将CAC与等位基因拷贝数进行回归分析，在0.05显著性水平上进一步证实了D10S189和D6S1053，其中将个体血统用作遗传背景协变量以控制非裔美国人中可能存在的分层现象。基于本研究及其他独立研究的结果来看，位于6号染色体80cM处（6q12）的D6S1053位置似乎蕴藏着一个极具潜力的动脉粥样硬化数量性状基因座。
