We used the PRS-CS “auto” version (28) to compute polygenic scores (PRSs) for the latent genetic AUDIT factors (Consumption and Problems) and their sum score counterparts (AUDIT-C and AUDIT-P) in European subjects from two independent samples: (i) an independent subset of unrelated individuals of European ancestry in the UK Biobank who did not fill out the AUDIT, and (ii) a subset of individuals of European ancestry from the Collaborative Study on the Genetics of Alcoholism (COGA)(29), which includes probands meeting criteria for alcohol dependence, their family members, and community control families. Using the ‘score’ algorithm in PLINK v1.90, we computed individual-level PRS to predict additional alcohol phenotypes (drinking quantity, drinking frequency, and lifetime AUD diagnosis) measured in UK Biobank and COGA (Supplementary Material 7). We tested for associations between AUDIT PRSs and alcohol phenotypes using linear (quantity and frequency phenotypes) or logistic (AUD) regression models in R v3.6.3. In UK Biobank, we included sex, age at first assessment, Townsend Deprivation Index score (30) and the first 10 ancestry principal components as covariates. In COGA, we included age, sex, array type,
