One phenotype where we would expect to find compelling evidence for gene-environment interaction effects is the alcohol dependence phenotype, considering its strong association in the parental generation with childhood environmental adversities in the offspring generation and heightened opportunities for social learning of excessive consumption patterns. It is plausible, but arguably not yet convincingly established, that greater consideration of such GXE effects will facilitate the goals of identifying more of the genes that are contributing to risk of alcohol dependence, as well as of understanding how (including under which environmental conditions) they are having effects. In these undertakings, however, it is critical to remember that much of the genetic effects on alcohol dependence appear to represent broad liabilitities to a range of externalizing behaviors and other substance dependence. This suggests that understanding relevant GXE interactions for alcohol dependence may involve studying nonspecific genes and environmental exposures and not focusing exclusively on alcohol-related phenotypes. Characterizing relevant endophenotypes that can be generalized across species and that are relevant to multiple behavior problems would be advanced, but further delineation of the relevant neurocircuitry and behavioral processes that are believed to subserve alcohol dependence more specifically would still be needed.
