Some limitations of this sample are also noteworthy. First, we restricted our analyses here to individuals of European American descent because the discovery GWAS was limited to individuals of European ancestry, and cross-ancestral predictions have several limitations (Martin et al., 2017). Second, despite being fairly large and predominantly ascertained for families with many alcohol dependent individuals, the COGA sample size may still be underpowered to detect the very modest percentages of variance explained by common SNPs for alcohol-related traits (Bogdan et al., 2018; Clarke et al., 2017; Gratten et al., 2014; Sanchez-Roige et al., 2017; Walters et al., 2018). In particular, although certain types of interaction (e.g. cross-over effects) do not necessitate significant main effects, we were likely under-powered to test such interactions with PRS where a main effect of PRS was undetectable.
