STATISTICAL METHOD FOR GENE/ENVIRONMENT INTERACTION AND GENETIC SUSCEPTIBILITY

该项目旨在开发新的统计工具 并将现有的评价指标应用于基因环境评价 相互作用和遗传易感性。工作分两步进行 领域：（1）改进流行病学研究设计，（2）设计 一种统计建模的方法来提高我们的检测能力， 基因型-暴露相互作用。遗传学家建议使用 病例及其父母（病例-父母三联体）研究遗传效应 在克服人口问题的同时， 分层或混合。如果一个种群由若干个 不同的亚群，基线疾病率不同， 遗传变异的频率，病例对照研究可能会发现， 变异与缺乏病因学的疾病之间的关联 仅仅因为不同的特征而产生的进口 亚群。案例-父三元组设计可以消除此类 潜在的误导性联想。我们正在研究的设计， 用控制父母三元组来增加病例父母三元组。这样的设计 应该将对混合物的保护扩展到检查 基因型和暴露联合。基因型-环境相互作用 当基因具有两个以上的等位基因时变得难以检测， 部分原因是描述相互作用需要许多参数。 我们已经提出了一种方法来参数化相互作用 这使得调查人员能够发现某些 传统方法可能忽略的互动。

This project seeks to develop new statistical tools and to apply existing ones in evaluating gene-environment interactions and genetic susceptibility. Work proceeded in two areas: (1) improving epidemiologic study designs, and (2) devising a statistical modeling approach to enhance our ability to detect genotype-exposure interactions. Geneticists have proposed using cases and their parents (case-parent triads) to study genetic effects on disease risk while overcoming the problem of population stratification or admixture. If a population consists of a number of distinct subpopulations that differ in baseline disease rates and in the frequency of a genetic variant, case-control studies may find associations between the variant and disease that lack etiologic import that arise simply because of the differing characteristics of the subpopulations. Case-parent triad designs can eliminate such potentially misleading associations. We are examining designs that augment case-parent triads with control-parent triads. Such designs should extend protection against admixture to studies that examine genotype and exposure jointly. Genotype-environment interactions become difficult to detect when genes have more than two alleles, in part because describing interactions requires many parameters. We have proposed a way to parameterize interactions parsimoniously that allows investigators to detect certain interactions that traditional methods could miss.