We find that GPS derived from markers associated with ethanol Consumption and MaxDrinks at modest p-value thresholds (p < 0.05 and above) predict those same outcomes in the ALSPAC sample. These results are consistent with the highly polygenic nature of alcohol phenotypes. Although GPS derived from relatively few markers (several hundred to ~25,000 for up to p < 0.01) were not predictive of outcome, those that are more inclusive do capture meaningful genetic liability. Furthermore, this interpretation is consistent with the null results of our replication attempts for markers with q < 0.50. Thus, it is likely that many of the variants implicated at marginal thresholds are incrementally contributing to risk, though to a degree too small to be detected in isolation. We observe similar trends when GPS are derived from the European ancestry group only, though results are less robust (Supplementary Table 3). We likely benefitted from the improved statistical power of the meta-analysis. These findings also provide support for the hypothesis that genetic variants impacting alcohol outcomes are largely similar across different ethnicities, though given variation with respect to allele presence/frequencies there are also likely to be ethnicity-specific genetic factors.
