Attention to endophenotypes as developmental phenomena may also provide additional insight into the pathways between genetic predispositions and eventual disorder. To date, the criterion for an endophenotype to be associated with the illness has typically been met using cross-sectional studies that compare individuals with AUD to healthy controls. However, there are also likely to be endophenotypes that emerge or maximally differentiate between those who will and will not go on to have AUD at points earlier in development. In a conceptual example of this, variation in the AUD-associated gene GABRA2 is also associated with childhood conduct disorder symptoms [127] and increased risk (odds ratios ranging from 2.1 to 2.7) of exhibiting an elevated persistent trajectory of externalizing behavior across adolescence and early adulthood [128]. Neither conduct disorder nor externalizing behavior trajectories meet the endophenotype criteria; however, what this example illustrates is the possibility that there may be endophenotypes earlier in development that predict adult AUD, and these can be capitalized on in gene identification efforts.
