Two-stage testing procedures with independent filtering for genome-wide gene-environment interaction
Two-stage testing procedures with independent filtering for genome-wide gene-environment interaction
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DOI：
10.1093/biomet/ass044
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发表时间：
2012-12-01
期刊：
影响因子：
2.7
通讯作者：
Prentice, Ross L.
中科院分区：
文献类型：
--
作者：
Dai, James Y.;Kooperberg, Charles;Prentice, Ross L.
已经提出了几种两阶段多重测试程序来检测全基因组关联研究中的基因-环境相互作用。在本文中，我们阐明了这些程序的有效性和功效所需的一般条件，并建议在随机临床试验中使用基因治疗相互作用的仅病例估计器来扩展两阶段程序。我们开发了一种统一的估计方程方法来证明一系列情况下过滤统计量和交互检验统计量之间的渐近独立性，包括具有规范链接的广义线性模型中的边际关联和交互。我们评估了妇女健康倡议临床试验中各种两阶段程序在模拟和遗传研究中的表现。
Several two-stage multiple testing procedures have been proposed to detect gene-environment interaction in genome-wide association studies. In this article, we elucidate general conditions that are required for validity and power of these procedures, and we propose extensions of two-stage procedures using the case-only estimator of gene-treatment interaction in randomized clinical trials. We develop a unified estimating equation approach to proving asymptotic independence between a filtering statistic and an interaction test statistic in a range of situations, including marginal association and interaction in a generalized linear model with a canonical link. We assess the performance of various two-stage procedures in simulations and in genetic studies from Women's Health Initiative clinical trials.