Efficient Two-Step Testing of Gene-Environment and Gene-Gene Interactions in Genome-Wide Association Studies

• Activity Number: 441
• Type: Invited
• Date/Time: Wednesday, August 3, 2011 : 8:30 AM to 10:20 AM
• Sponsor: Section on Statistics in Epidemiology
• Author(s): Cassandra Elizabeth Murcray*+ and Duncan Thomas and Juan Pablo Lewinger and W. James Gauderman
• Companies: University of Southern California and University of Southern California and University of Southern California and University of Southern California
• Keywords: GWAS ; gene-gene interaction ; gene-environment interaction ; case-control ; case-parent trios

Abstract

Recently developed methods to detect interactions in GWA studies have shown increased power relative to traditional approaches. Two-step analyses have been proposed to prioritize the large number of SNPs tested to highlight those likely to be involved in GxE/GxG interactions. Kooperberg and LeBlanc (2008) suggested screening on genetic marginal effects in a search for GxG interactions. Alternatively, Murcray et al (2009) suggested screening SNPs by testing the G-E association induced by an interaction in the combined case-control sample. Gauderman et al (2010) proposed a screening step based on the association between parental genotypes and case exposure in GWA studies in case-parent trios. In these methods, SNPs that pass the respective screening step at a liberal significance threshold are followed up with a formal test of interaction in the second step. For case-control data, we show that the Murcray et al approach is often the most efficient method, but that a hybrid method that combines the Murcray et al and Kooperberg et al methods by allocating a proportion of the experiment-wise significance level to each test is a powerful and robust method for nearly any underlying model.