Population Stratification in a Case-Control Study of Brain Arteriovenous Malformation in Latinos
Population Stratification in a Case-Control Study of Brain Arteriovenous Malformation in Latinos
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DOI：
10.1159/000160215
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发表时间：
2008-01-01
影响因子：
5.7
通讯作者：
Young, William L.
中科院分区：
文献类型：
--
作者：
Kim, Helen;Hysi, Pirro G.;Young, William L.
背景：在混合群体中进行的遗传关联研究可能会因群体分层而导致虚假关联而混淆。本初步研究的目的是在脑动静脉畸形（BAVM）的病例对照研究中确定人群分层的存在和影响。方法：我们在自我报告的拉丁裔种族/民族的BAVM病例和健康对照中检测了83个血统信息标记（n = 294）。个体祖先估计（IAE）使用结构程序，假设3个潜在的亚群。Summary chi(2)采用比较祖先信息标记基因型频率的检验来检测分层，并将IAE作为协变量纳入逻辑回归分析，以解释遗传背景的差异。结果：拉丁美洲人（47%的美洲原住民，45%的欧洲血统和8%的非洲血统）的混合估计揭示了祖先群体内个体之间的异质性。摘要chi(2)检验显著（p = 0.005），提示病例与对照组存在祖先差异。此外，遗传祖先与IL-6基因（IL-6- 174g >C）启动子变异的频率差异有关。平均而言，IL6-174 GG基因型的受试者有6%以上的美洲原住民血统（p = 0.023）。与IL-6-174 GG基因型相关的经年龄和性别调整的BAVM风险为1.85 (95% CI 0.99-3.48, p = 0.055)，进一步调整IAE的OR为1.96 （95% CI 1.03-3.72, p = 0.039）。结论：考虑到祖先背景的差异，IL-6-174G>C多态性与拉丁美洲人患BAVM的风险增加有关。这些结果提示了微妙的、负面的混淆，并说明了在混合人群中进行的病例对照研究中解决人口分层的重要性。版权所有2008 S. Karger AG，巴塞尔
Background: Genetic association studies conducted in admixed populations may be confounded by population stratification resulting in spurious associations. The purpose of this pilot study was to determine the presence and effect of population stratification in a case-control study of brain arteriovenous malformation (BAVM). Methods: We tested 83 ancestry informative markers in BAVM cases and healthy controls of self-reported Latino race/ethnicity (n = 294). Individual ancestry estimates (IAE) were obtained using the Structure program, assuming 3 underlying subpopulations. Summary chi(2) tests comparing genotype frequency of ancestry informative markers were used to detect stratification and IAE were included as covariates in logistic regression analysis to account for differences in genetic background. Results: Admixture estimates for Latinos (overall 47% native American, 45% European and 8% African ancestry) revealed heterogeneity between individuals within ancestral groups. The summary chi(2) test was significant (p = 0.005), suggesting ancestral differences between cases and controls. Furthermore, genetic ancestry was associated with frequency differences in a promoter variant in the IL-6 gene (IL-6-174G>C). On average, subjects with the IL6-174 GG genotype had 6% greater Native American ancestry (p = 0.023). Age-and sex-adjusted risk of BAVM associated with the IL-6-174 GG genotype was 1.85 (95% CI 0.99-3.48, p = 0.055), and further adjustments for IAE yielded an OR of 1.96 (95% CI 1.03-3.72, p = 0.039). Conclusion: The IL-6-174G>C polymorphism was associated with increased risk of BAVM among Latinos after accounting for differences in ancestral background. These results suggest subtle, negative confounding and illustrate the importance of addressing population stratification in case-control studies conducted in admixed populations. Copyright (C) 2008 S. Karger AG, Basel