The endophenotype concept was initially proposed as a strategy for improving gene identification in view of the complex and heterogeneous nature of psychiatric disorders. In the area of alcohol research, level of response to alcohol and resting and event-related neurophysiological measures have received considerable attention as candidate endophenotypes, and have also led to replicable genetic associations (e.g., CHRM2 [7] and GABRA2 [115]) for AUD. As these examples illustrate, the past successes of endophenotype strategies for AUD gene identification suggest that the concept will continue to remain relevant to AUD research today, even as gene identification efforts move towards large-scale phenotyping at the diagnostic level. A number of other candidate endophenotypes show promise, including delayed reward discounting, executive functions, sweet liking, and structural brain features. Systematic efforts to continue to refine and validate these as elected endophenotypes, and to identify the genes, polygenes, and gene networks that may influence variation in these traits/behaviors (and in turn AUD) by themselves and in the context of environmental exposures (particularly alcohol) represent important directions for future research.
