A number of human laboratory studies employing behavioral pharmacology and experimental designs have examined the effect of the Asn40Asp SNP in a host of alcohol-related phenotypes, including alcohol craving, subjective intoxication, stress-induced drinking, and appetitive action-tendencies. These studies offer an advantage to case–control genetic studies in that experimental phenotypes are putatively closer to the neurobiology of alcoholism (Ray et al., 2010b,c) and laboratory designs can more easily control extraneous variables. Specifically, experimental approaches allow for manipulation and assessment of critical components of alcoholism that are more proximal to the underlying neurobiology of the disorder, such as mechanisms of alcohol-induced reward (“liking”) and craving (“wanting”) (Ducci and Goldman, 2008). These traits may in fact represent endophenotypes or intermediate phenotypes for alcoholism (Hines et al., 2005). Moreover, given that alcohol dependence is highly heterogeneous in terms of both clinical phenomenology and causal pathways, more focused studies may be more effective at parsing discrete translational phenotypes and their underlying genetic bases. Ultimately, however, the utility of such studies hinges upon their ability to effectively inform clinical practice, such as disorder etiology and treatment outcome.
