Update on the State of the Science for Analytical Methods for Gene-Environment Interactions

The analysis of gene-environment interaction (G×E) may hold the key for further understanding the etiology of many complex traits. The current availability of high-volume genetic data, the wide range in types of environmental data that can be measured, and the formation of consortiums of multiple studies provide new opportunities to identify G×E but also new analytical challenges. In this article, we summarize several statistical approaches that can be used to test for G×E in a genome-wide association study. These include traditional models of G×E in a casecontrol or quantitative trait study as well as alternative approaches that can provide substantially greater power. The latest methods for analyzing G×E with gene sets and with data in a consortium setting are summarized, as are issues that arise due to the complexity of environmental data. We provide some speculation on why detecting G×E in a genome-wide association study has thus far been difficult. We conclude with a description of software programs that can be used to implement most of the methods described in the paper.