To our knowledge, no GEWIS of depression has been published to date. Though research on GEWIS of depression and other psychiatric phenotypes is lacking, a small but emerging body of research on other complex phenotypes suggests GEWIS can yield important new gains. For example, studies have identified significant genome-wide GxE interactions in cancer,131,132 diabetes133 and insulin resistance,134 Parkinson's disease 135, pulmonary function 136, and nonsyndromic cleft palate.137 While interest in GEWIS is growing, there are several challenges to conducting this type of study.129 The first is identifying the best methods to test for genome-wide GxE. Several methodological approaches have been developed (see for example reviews by 138,139); however there is no consensus on what methods are most ideal. Selection of a specific analytic method depends largely on whether the goal is to leverage GxE to discover novel loci or characterize the joint effect of genetic variants and environmental factors.140
