These findings should be interpreted in light of several limitations. Regretfully, AUDIT is a self-report that can be influenced by misreporting, and it only captures alcohol use in the past year, so can be influenced by longitudinal changes in drinking that may be a consequence, for example, of other illnesses (44). People who stopped drinking or never drinkers might represent genetically distinct groups; in our dataset 4,511 individuals were never drinkers, and 4,290 were previous drinkers. While our approach has substantially reduced bias in AUDIT without excluding any individuals from discovery, future studies might consider employing multiple techniques (e.g., separate never drinkers from former drinkers) to further alleviate potential biases associated with frequency of alcohol use in population-based cohorts. Additionally, while the AUDIT PRSs tended to perform similarly in UK Biobank and COGA, the portability of PRSs can be influenced by demographic characteristics such as the socio-economic status, age or sex (45). It remains to be determined how generalizable the genetics of AUDIT are across different populations, especially in samples of different ancestries (as we have only included individuals of
