One possible reason for the different outcomes between our study and the earlier studies is that we used stressors in adulthood and not childhood. For example, Binder et al. (2008) in an analysis of the HPA axis FKBP5 gene showed a G × E effect on posttraumatic stress disorder for childhood trauma but not for adult stressors (Binder et al., 2008). It has been shown that significant childhood trauma has a deleterious and permanent effect on the development and functioning of the extra hypothalamic CRF system (Enoch, 2010). Stressors in adulthood may work by different mechanisms. We did not have adequate data on exposure to childhood trauma in the SAGE dataset. Nevertheless, since early life stress is a predictor of adult psychopathology including alcoholism (Enoch, 2010), it is likely that a significant proportion of the alcoholics had been exposed to childhood trauma. Moreover, several studies have shown that exposure to childhood trauma predicts increased risk for subsequent trauma in adulthood including physical assault and rape (Enoch, 2010). Sample differences may account for the null findings in the Kranzler et al. (2011) study for interactive effects of the TAT haplotype and childhood trauma on lifetime risk of alcoholism.
