Examining population stratification via individual ancestry estimates versus self-reported race
Examining population stratification via individual ancestry estimates versus self-reported race
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DOI：
10.1158/1055-9965.epi-04-0832
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发表时间：
2005-06-01
影响因子：
3.8
通讯作者：
Schwartz, AG
中科院分区：
文献类型：
--
作者：
Barnholtz-Sloan, JS;Chakraborty, R;Schwartz, AG
群体分层有可能影响遗传标记研究的结果。在复杂疾病的病例对照研究中，估计个体祖先提供了一种连续的测量方法来评估人口结构，而不是使用自我报告的种族群体。在一项早发性肺癌病例对照研究中，我们使用联邦调查局CODIS核心短串联重复序列13个位点，采用两种不同的分析方法估计个体祖先。使用已发表的等位基因频率估计“欧洲”和“西非”群体的个体祖先比例。大多数高加索人、非西班牙裔人有> 50%的欧洲血统，而大多数非裔美国人有< 20%的欧洲血统，无论血统估计方法如何，尽管自我报告的种族和血统也存在显著重叠。当我们进一步研究血统和自我报告的种族对肺癌风险基因型频率的影响时，我们发现GSTM 1无效基因型的频率因个体欧洲血统和自我报告的种族内的病例对照状态而异（特别是非洲裔美国人）。遗传风险模型显示，与没有组调整或自我报告种族调整的模型相比，调整欧洲血统个体提供了更好的数据拟合。这项研究表明，存在显着的人口亚结构差异，自我报告的种族单独不捕获和个人祖先可能与疾病状态和/或候选基因风险基因型混淆。
Population stratification has the potential to affect the results of genetic marker studies. Estimating individual ancestry provides a continuous measure to assess population structure in case-control studies of complex disease, instead of using self-reported racial groups. We estimate individual ancestry using the Federal Bureau of Investigation CODIS Core short tandem repeat set of 13 loci using two different analysis methods in a case-control study of early-onset lung cancer. Individual ancestry proportions were estimated for "European" and "West African" groups using published allele frequencies. The majority of Caucasian, non-Hispanics had > 50% European ancestry, whereas the majority of African Americans had < 20% European ancestry, regardless of ancestry estimation method, although significant overlap by self-reported race and ancestry also existed. When we further investigated the effect of ancestry and self-reported race on the frequency of a lung cancer risk genotype, we found that the frequency of the GSTM1 null genotype varies by individual European ancestry and case-control status within self-reported race (particularly for African Americans). Genetic risk models showed that adjusting for individual European ancestry provided a better fit to the data compared with the model with no group adjustment or adjustment for self-reported race. This study suggests that significant population substructure differences exist that self-reported race alone does not capture and that individual ancestry may be confounded with disease status and/or a candidate gene risk genotype.