STATISTICAL METHOD FOR GENE/ENVIRONMENT INTERACTION AND GENETIC SUSCEPTIBILITY

工作总结：该项目寻求开发新的统计工具和 应用现有的方法评价基因与环境的相互作用 遗传易感性。开展了三个方面的工作：(一)改进 流行病学研究设计，(2)设计统计建模方法 为了提高数据分析员检测基因暴露的能力 交互作用，以及(3)结合已发表研究的结果以更好地 评估维生素D受体与维生素D受体之间的关系 多态和骨密度。 如果基因分型控制对象不情愿，他们可能不可行。 捐献组织或担心Genetic的隐私 信息。在通常看似合理的假设下，基因和 暴露在研究人群中是独立的，我们发现研究 未对对照进行基因分型的设计可以使用比 其他设计，以达到相同的精度，以估计暴露和 基因型-暴露交互作用的影响。为了估计基因的影响， 然而，这需要关于基因流行率的外部数据。 基因与环境的相互作用变得很难检测 有两个以上的等位基因，部分原因是描述了相互作用 需要许多参数。我们已经提出了一种参数化的方法 节俭的互动，使调查人员能够检测到某些 传统方法会忽略的交互作用。 结合16项研究的结果，我们发现了多态现象的证据 在维生素D受体基因中与大约2.5%的下降有关 在骨矿密度方面。

Summary of Work: This project seeks to develop new statistical tools and to apply existing ones in evaluating gene-environment interactions and genetic susceptibility. Work proceeded in three areas: (1) improving epidemiologic study designs, (2) devising a statistical modeling approach to enhance a data analyst's ability to detect genotype-exposure interactions, and (3) combining results from published studies to better assess the putative relationship between a vitamin D receptor polymorphism and bone density. Genotyping control subjects may not be feasible if they are reluctant to contribute tissue or have concerns about privacy with genetic information. Under the often-plausible assumption that genotype and exposure are independent in a study population, we found that study designs where controls are not genotyped can use fewer subjects than other designs to achieve the same precision in estimating exposure and genotype-exposure interactions effects. To estimate genotype effects, however, requires external data about gene prevalence. 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 would miss. Combining results from 16 studies, we found evidence that a poly-morphism in the vitamin D receptor gene was associated with about a 2.5% decline in bone mineral density.