Endophenotypes for Alcohol Use Disorder: An Update on the Field

Curr Addict Rep. 2015 Mar;2(1):76-90. doi: 10.1007/s40429-015-0046-y.


The endophenotype concept was first proposed as a strategy to use (purportedly) genetically simpler phenotypes in gene identification studies for psychiatric disorders, and is distinct from the closely related concept of intermediate phenotypes. In the area of alcohol use disorder (AUD) research, two candidate endophenotypes have produced replicable genetic associations: level of response to alcohol and neurophysiology markers (e.g., event-related oscillations and event-related potentials). Additional candidate endophenotypes from the cognitive, sensory, and neuroimaging literatures show promise, although more evidence is needed to fully evaluate their potential utility. Translational approaches to AUD endophenotypes have helped characterize the underlying neurobiology and genetics of AUD endophenotypes and identified relevant pharmacological interventions. Future research that capitalizes on the polygenic nature of endophenotypes and emphasizes endophenotypes that may change across development will enhance the usefulness of this concept to understand the genetically-influenced pathways toward AUD.

Keywords: Endophenotypes; addictions; alcohol use disorder; brain function; brain structure; delayed reward discounting; genetics; genomics; sweet liking.