A corollary of this point, which is particularly relevant for substance use disorder candidate endophenotypes, is that there is likely to be a dynamic relationship between the genes associated with AUD and a necessary environmental exposure (i.e., alcohol). For example, ethanol exposure induces modest differential gene expression in lymphoblastoid cell lines from alcoholics and non-alcoholics [129]. The possibility of identifying AUD genetic predispositions that interact with environmental factors (e.g., adolescent alcohol exposure) to produce variation in a candidate endophenotype is particularly promising. For example, adolescent alcohol exposure may initiate a cascade of biological changes (e.g., gene expression [130]) that contribute to variation in AUD candidate endophenotypes and eventual disorder.
