STATISTICAL METHOD FOR GENE/ENVIRONMENT INTERACTION AND GENETIC SUSCEPTIBILITY

该项目旨在开发新的统计工具来评估基因-环境相互作用和遗传易感性。改进研究设计方面的工作已经开始。遗传学家在克服群体分层或混杂问题的同时，提出利用病例及其父母（病例-父母三联组）来研究遗传对疾病风险的影响。如果一个种群由若干不同的亚种群组成，这些亚种群在基线发病率和基因变异频率上存在差异，则病例对照研究可能会发现该变异与疾病之间存在关联，而这种关联仅仅是因为亚种群的特征不同而产生的，因此缺乏病因学意义。案例-父母三位一体设计可以消除这种潜在的误导性联系。我们研究了研究基因-环境相互作用的病例-父母数据分析方法，发现常用的方法是无效的。我们提出了一种基于对数线性模型的方法，当通常的方法失败时，它提供了有效的推理。我们也在研究用控制双亲三元组来增加case-parent三元组的设计，以克服单独使用case-parent三元组的一些缺点。这种设计应该更充分地将对种群结构的保护扩展到基因型和暴露的研究。

This project seeks to develop new statistical tools for evaluating gene-environment interactions and genetic susceptibility. Work has proceeded in the area of improving study designs. Geneticists have proposed using cases and their parents (case-parents 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 arise simply because of the differing characteristics of the subpopulations and, consequently, lack etiologic import. Case-parents triad designs can eliminate such potentially misleading associations. We have investigated ways to analyze case-parents data for studying gene-environment interaction and found that a commonly used approach is invalid. We have proposed an approach based on loglinear models that provides valid inference when the usual approach fails. We are also investigating designs that augment case-parents triads with control-parent triads to overcome some shortcomings of using case-parents triads alone. Such designs should more fully extend protection against population structure to studies of genotype and exposure together.