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首页> 外文期刊>Annals of Human Genetics >Attributing Hardy-Weinberg disequilibrium to population stratification and genetic association in case-control studies.
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Attributing Hardy-Weinberg disequilibrium to population stratification and genetic association in case-control studies.

机译：在病例对照研究中，将Hardy-Weinberg不平衡归因于人口分层和遗传关联。

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Loci exhibiting Hardy-Weinberg disequilibrium (HWD) are often excluded from association studies, because HWD may indicate genotyping error, population stratification or selection bias. For case-control studies, HWD can result from a genetic effect at the locus. We extend the modelling to accommodate both stratification and genetic effects. Theoretical genotype frequencies and HWD coefficients are derived under a general genetic model for a population with two strata. Maximum likelihood is used to estimate model parameters and a test for lack of fit identifies the models most consistent with the data. Simulations were used to assess the method. The technique was applied to a group of ethnically and clinically heterogeneous kidney stone formers and controls, both exhibiting HWD for the R990G SNP of the CASR gene. Results indicate the best fitting model incorporates both stratification and genetic association. The ability of our method to apportion HWD to stratification and genetic effects may well be a significant advance in dealing with heterogeneity in case-control genetic association studies.
机译：表现出Hardy-Weinberg不平衡（HWD）的位点通常被排除在关联研究之外，因为HWD可能指示基因分型错误，人群分层或选择偏向。对于病例对照研究，HWD可以由所在地的遗传效应产生。我们扩展了模型以适应分层和遗传效应。理论基因型频率和HWD系数是在具有两个阶层的总体遗传模型下得出的。最大似然用于估计模型参数，缺乏适合性的测试可确定与数据最一致的模型。仿真用于评估该方法。该技术已应用于一组种族和临床上异质的肾结石形成者和对照者，均对CASR基因的R990G SNP表现出HWD。结果表明最佳拟合模型结合了分层和遗传关联。我们的方法将HWD分配给分层和遗传效应的能力很可能是在病例对照遗传协会研究中处理异质性的重要进展。

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