Using four independent samples with clinical assessments of problem alcohol use behaviors, we found a differential prediction of polygenic scores for alcohol problems across clinically ascertained samples and population-based epidemiological samples. We found significant cross-prediction within our two population-based birth cohort samples, with aggregate genetic variants identified in ALSPAC predicting AUDs in FT12, albeit only contributing to a small identifiable proportion of the variance. However, similar scores derived from ALSPAC did not predict risk for AUDs in either of two clinically ascertained samples (COGA; IASPSAD), despite COGA having a sample size nearly double that of FT12. Cross-sample polygenic risk prediction based on the other three discovery GWAS weights were less conclusive, with no significant risk prediction found within the two clinically ascertained samples or between any pair of samples from different types. We observed a consistent trend towards positive cross-prediction within sample types but null or negative prediction from population-based samples to clinically ascertained samples and vice versa, but this effect requires replication given the lack of robust statistical support. The consistency in the pattern of results in two samples from each type encourages confidence.
