Additional study strengths are noted. Since the lack of robust genetic main associations is a major challenge for GxE research in psychiatric disorders (Duncan & Keller, 2011), we investigated a genetic risk factor with such a robust effect, which yielded positive GxE results. Second, ADH1B directly affects alcohol metabolism, which is a pathway to alcohol-related phenotypes that is better understood than the genes affecting neuronal pathways that have been the main focus of previous SUDs G×E literature (Young-Wolff et al., 2011). Finally, we used graded alcohol phenotype variables (Maxdrinks and AUD severity). These typically have more statistical power to detect associations (Kuo et al., 2008; Waldman et al., 1999), and our use of them is consistent with a general movement in psychiatry to address dimensional rather than binary phenotypes (Ehlke et al., 2012; Hasin et al., 2012)., These strengths enhance the possibility of successful replication in a similarly powered sample (i.e., moderate ADH1B-rs1229984 prevalence and informative phenotypes), which has been challenging in GxE studies of SUDs (Duncan & Keller, 2011).
