One prior study suggested the polygenic prediction is maximized when the discovery and target cohort have similar demographic characteristics and ascertainment strategies (Savage et al., 2018). Thus, it is also possible that the variance associated with the PRS is greater in the subset of COGA that is demographically matched to the UK Biobank participants (e.g., older age). However, age did not appear to moderate the association between the PRS and alcohol-related outcomes in the current study, nor was there support for absence of proportionality of hazards in the survival model, suggesting homogeneity of effects across age. Relatedly, even though family history was a strong predictor of problem drinking, we found no evidence that it moderated the effect of the PRS in our sample. This might be due to the partially high-risk nature of the COGA sample. Despite differences between the characteristics of the discovery sample and COGA, we detected appreciable variance in alcohol use.
