Here we presented a comprehensive review of the information available from molecular databases and current literature regarding the role of ADH1B in alcohol use disorders and more generally, in the human phenome. The majority of the evidence is focused on how ADH1B non-synonymous substitutions (rs1229984 and rs2066702), associated with increased catalytic activity, are associated with large effects on alcohol sensitivity, which consequently affects drinking behaviors and long-term consequences of alcohol use. However, some aspects of this alcohol-related cascade need additional study. For instance, ADH1B protective alleles seem to have a reduced effect on alcohol drinking behaviors in subjects exposed to a negative social environment [Meyers and others 2015; Olfson and others 2014; Sartor and others 2014]. Investigating subjects with high alcohol sensitivity may facilitate the identification of loci that interact with social environment in determining alcohol drinking behaviors. Another example is related to the role of ADH1B in the predisposition to cancer: it is not clear whether this association is mediated by alcohol use, by alcohol metabolism in non-hepatic tissues, or by both mechanisms. Furthermore, the analysis of ADH1B protein networks with genome-wide data can contribute to clarifying the pathogenic pathways by which alcohol contributes to carcinogenesis.
