What specific genetic loci in combination with specific environmental contexts provide the most information about an individual's likelihood of exhibiting a particular behavior at a particular time in his or her life? This question is critical to both social and genetic epidemiologists because it suggests that environmental influences depend on an individual's genetic composition and that genetic influences are contingent on the social environment in which one resides, works, and plays. Little debate exists about the relevance of this question, but finding an answer has thus far proven to be quite difficult. There is little consensus on what constitutes the environment, little agreement regarding statistical versus substantive significance of interactions, little consensus about social and genetic theories explaining the mechanisms of gene-environment interplay, and a replication record that is only marginally better than chance (Risch et al. 2009). Our results suggest that these concerns may be more important when extended to the genome-wide scale. Our results do not challenge the relevance of GWAS studies, nor do they challenge GxE studies in general. Rather, we believe that the SNP-by-SNP GxE approach
