title: Two-stage testing procedures with independent filtering for genome-wide gene-environment interaction.
abstract: 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.
authors.affiliation: Public Health Science Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, U.S.A. , jdai@fhcrc.org.
authors.forename: James Y
authors.initials: JY
authors.lastname: Dai
authors.forename: Charles
authors.initials: C
authors.lastname: Kooperberg
authors.forename: Michael
authors.initials: M
authors.lastname: Leblanc
authors.forename: Ross L
authors.initials: RL
authors.lastname: Prentice
keywords: Case-only estimator; Filtering; Gene-treatment interaction; Multiple testing; Pharmacogenetics; Randomization