A large number of genes have been studied as candidates for AD risk and the list is rapidly expanding with results from high-density marker arrays (e.g., genome-wide association studies). However, in the studies we reviewed, researchers typically utilized genes that were available in their existing datasets (e.g., the serotonin transporter gene) rather than selecting genes based on hypotheses of biological plausibility (e.g., genes influencing metabolism). The effects of a particular gene may be contingent on other genes (i.e., epistasis) (Enoch et al., 2010a; Huang et al., 2007; Lee et al., 2009; Skowronek et al., 2006), and it is interesting to consider whether unmeasured genes moderate the GxE processes that have been identified with respect to drinking behaviors (i.e., GxGxE). Unfortunately, most studies were underpowered to test for three-way interactions as evidence for epistasis.
