One approach to filling this gap may come from genome-environment wide interaction studies (GEWIS), pronounced “G-Whiz.”129,130 In a GEWIS, investigators test for statistical interaction or GxE, with the “G” defined as the genetic loci (e.g., SNPs) included in a GWAS and the “E” defined as a known environmental exposure. Unlike candidate gene GxE, GEWIS offers the opportunity to conduct a genetically unbiased search—that is, one in which prior genetic or biologic hypotheses are not required. In one type of GEWIS, investigators could focus on loci for which a main effect of a genetic variant has been established by GWAS. In this scenario, loci identified by GWAS become candidates for GxE analysis, but with the advantage over traditional candidate gene studies that the locus is already known to influence the phenotype of interest.
