Certain limitations should be considered in interpreting findings from the current study. First, the sample was composed of participants from several different studies that employed different study designs (e.g., case–control, high-risk family), resulting in an overrepresentation of heavy substance users in a heterogeneous sample. The prevalence of exposure to childhood adversity and endorsement of AUD symptoms and maxdrinks are therefore neither representative of clinical populations nor of the general population. However, as the association of genetic background and childhood adversity with alcohol outcomes would not be impacted by the heterogeneity of the sample or high concentration of childhood adversity and problem alcohol use, variability in the sample ascertainment does not limit interpretation of the key findings. Second, although preliminary phenotypic analyses supported conducting GxE analyses separately by sex as well as population, the resulting increase in tests raises the possibility of Type I error inflation. However, even after applying a Bonferroni correction for multiple testing within groups – a conservative adjustment given the nonindependence of the two alcohol outcomes – the GxE interaction in the EA male model remained statistically significant…
