Genetic ancestry, population sub-structure, and cardiovascular disease-related traits among African-American participants in the CARDIA Study
Genetic ancestry, population sub-structure, and cardiovascular disease-related traits among African-American participants in the CARDIA Study
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DOI：
10.1007/s00439-007-0350-2
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发表时间：
2007-06-01
期刊：
影响因子：
5.3
通讯作者：
Nickerson, Deborah A.
中科院分区：
文献类型：
--
作者：
Reiner, Alexander P.;Carlson, Christopher S.;Nickerson, Deborah A.
非洲裔美国人在基因上是混血的。在来自种族混合群体的无关个体中进行的研究可能既容易受到群体分层的混淆，又提供了通过混合连锁不平衡有效定位复杂性状的机会。通过分型42个祖先信息标记和估计遗传祖先，我们评估了青年冠状动脉风险发展(CARDIA)队列中非裔美国人参与者的基因混合和异质性。我们还评估了个体遗传血统与几个与心血管风险相关的数量性状和二元性状之间的关系。我们发现了群体亚结构和超额标记间连锁不平衡的证据，这与最近的混合一致。估计的群体混合比例为78.1%的非洲人和22.9%的欧洲人，但不同的地理区域有所不同。在多元回归模型中，非洲血统与总胆固醇降低、低密度脂蛋白-胆固醇降低和甘油三酯降低显著相关，也与胰岛素抵抗风险增加相关。这些观察到的非洲血统和几种血脂特征之间的关联符合非洲裔人比欧洲裔美国人拥有更健康的血脂谱的总体趋势。遗传血统与高血压、体重指数、腰围、C反应蛋白水平或冠状动脉钙化之间没有关联。这些结果表明，在涉及美国非裔美国人的大型研究中，基因关联与一些心血管疾病相关特征可能存在混淆。
African-American populations are genetically admixed. Studies performed among unrelated individuals from ethnically admixed populations may be both vulnerable to confounding by population stratification, but offer an opportunity for efficiently mapping complex traits through admixture linkage disequilibrium. By typing 42 ancestry-informative markers and estimating genetic ancestry, we assessed genetic admixture and heterogeneity among African-American participants in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort. We also assessed associations between individual genetic ancestry and several quantitative and binary traits related to cardiovascular risk. We found evidence of population sub-structure and excess inter-marker linkage disequilibrium, consistent with recent admixture. The estimated group admixture proportions were 78.1% African and 22.9% European, but differed according to geographic region. In multiple regression models, African ancestry was significantly associated with decreased total cholesterol, decreased LDL-cholesterol, and decreased triglycerides, and also with increased risk of insulin resistance. These observed associations between African ancestry and several lipid traits are consistent with the general tendency of individuals of African descent to have healthier lipid profiles compared to European-Americans. There was no association between genetic ancestry and hypertension, BMI, waist circumference, CRP level, or coronary artery calcification. These results demonstrate the potential for confounding of genetic associations with some cardiovascular disease-related traits in large studies involving US African-Americans.