Admixture mapping of quantitative trait loci for blood lipids in African-Americans
Admixture mapping of quantitative trait loci for blood lipids in African-Americans
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DOI：
10.1093/hmg/ddp122
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发表时间：
2009-06-01
影响因子：
3.5
通讯作者：
Risch, Neil J.
中科院分区：
文献类型：
--
作者：
Basu, Analabha;Tang, Hua;Risch, Neil J.
血脂水平，包括低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）和甘油三酯（TG），是高度遗传的特征，也是动脉粥样硬化性心血管疾病（CVD）的主要危险因素。利用对整个基因组标记位置的个体血统估计，我们对来自家庭血压计划的非裔美国人的大样本中的所有三种脂质特征进行了新颖的定量混合图谱分析。以总欧洲血统和特定标记位置的欧洲血统作为解释变量以及人口统计协变量进行回归分析。使用稳健排列分析来评估统计显着性。总体而言，欧洲血统与 HDL-C（负）和 TG（正）显着相关，但与 LDL-C 无关。我们发现了强有力的证据，证明 8q 染色体上有一个新的 HDL-C 基因座，该基因座与欧洲血统呈负相关 (P = .0014)；同一地点也显示出欧洲血统与甘油三酯水平呈正相关。 14q 染色体上的一个区域也显示 HDL-C 水平与欧洲血统之间存在显着的负相关。在染色体 15q 上，观察到欧洲血统与 TG 呈负相关，与 HDL-C 呈正相关。 LDL-C 的结果总体上不太显着。我们还发现了 HDL-C 和 TG 联合分布背后的全基因组血统效应的重要证据，但 8 号染色体上的基因座并未完全解释这一效应。我们的结果与遗传贡献一致，并可能解释黑人与白人中发现的更健康的 HDL-C 和 TG 谱。确定的区域为非洲裔美国人和可能的其他人群中脂质变异的遗传变异的后续研究提供了地点。
Blood lipid levels, including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG), are highly heritable traits and major risk factors for atherosclerotic cardiovascular disease (CVD). Using individual ancestry estimates at marker locations across the genome, we present a novel quantitative admixture mapping analysis of all three lipid traits in a large sample of African-Americans from the Family Blood Pressure Program. Regression analysis was performed with both total and marker-location-specific European ancestry as explanatory variables, along with demographic covariates. Robust permutation analysis was used to assess statistical significance. Overall European ancestry was significantly correlated with HDL-C (negatively) and TG (positively), but not with LDL-C. We found strong evidence for a novel locus underlying HDL-C on chromosome 8q, which correlated negatively with European ancestry (P = .0014); the same location also showed positive correlation of European ancestry with TG levels. A region on chromosome 14q also showed significant negative correlation between HDL-C levels and European ancestry. On chromosome 15q, a suggestive negative correlation of European ancestry with TG and positive correlation with HDL-C was observed. Results with LDL-C were less significant overall. We also found significant evidence for genome-wide ancestry effects underlying the joint distribution of HDL-C and TG, not fully explained by the locus on chromosome 8. Our results are consistent with a genetic contribution to and may explain the healthier HDL-C and TG profiles found in Blacks versus Whites. The identified regions provide locations for follow-up studies of genetic variants underlying lipid variation in African-Americans and possibly other populations.