Two-stage testing procedures with independent filtering for genome-wide gene-environment interaction

James Y. Dai, Charles Kooperberg, Michael Leblanc and Ross L. Prentice

Biometrika, 2012, vol. 99, issue 4, 929-944

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. Copyright 2012, Oxford University Press.

Date: 2012
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