This research has several important limitations. First, all analyses were limited to individuals of European ancestry because the discovery GWASs available were conducted in individuals of primarily European ancestry. It will be important to ascertain sizable samples of subjects with non-European ancestries to properly estimate the predictive utility of PRS in non-European samples. This is especially important for racial-ethnic minorities so that health disparities are not further perpetuated40. Second, our use of lifetime diagnoses may obscure the impact of changing genetic influences on the development of AUD across the life course41,42. Future work should draw on longitudinal data to examine the ways in which the strength of associations for PRS changes with the age of the target sample. Third, UKB was a large portion of the discovery sample for each of the GWAS used to create PRS. To the degree that UKB is biased, each of the PRS in these analyses will also reflect that bias43. Finally, these analyses examined the marginal influence of PRS, independent of environment. Processes of gene-environment interaction (GxE) are well documented in alcohol misuse44–47. Incorporating
