drinking was defined as having five or more alcoholic drinks within a 24-hour period, which is a more stringent threshold for females where four drinks are considered the typical threshold. Hence, sex differences regarding genetic and environmental influences on trajectories of heavy episodic drinking could not be explicitly tested in the current analyses, although separate analytic models were conducted for males and females. Using sex-specific cutoffs (i.e., according the standard definitions of binge drinking) may potentially lead to a more consistent pattern of results for males and females. Additionally, given sex differences in heritability estimates for alcohol use problems (King et al., 2005), it is possible that different genes may be involved for alcohol-related phenotypes in males and females. Future studies may consider conducting GWAS separately for males and females, so that PRS are sex-specific. Finally, the findings may not be generalizable as the analyses were limited to European-Americans. Recent evidence suggests that the association of alcohol dependence and specific genetic variants may differ between racial-ethnic groups (Gelernter et al., 2014).
