of individuals with the highest PRS as the high PRS group and compared with the remaining 90% of individuals. For comparison purposes, we also performed analyses using the original continuous PRS scores (i.e., not dichotomized). For testing the associations between DSM-5 AUD diagnostic criterion count and PRS, continuous PRS scores were used. To test for interactions between PRS and family history, as well as whether PRS were still significant after accounting for family history, we also fit models which included PRS, family history, and their interactions. Sex and birth cohorts (a better predictor of AUD than age in COGA (Grucza et al., 2008, Lai et al., 2020)), and the first 10 principal components of population stratification were included as covariates in all analyses. Birth cohorts were defined based on birth year as follows: 1890–1929, 1930–1949, 1950–1969, ≥1970. As COGA samples were genotyped on different arrays, genotype array indicator was also included in all PRS analyses. There were two phenotypes (AUD and DSM-5 AUD diagnostic criterion count) and we tested four groups of samples (full sample, FH+, FH?, and FH−); therefore, we adjusted for multiple testing with the significance threshold defined as 0.05/8=6.25E-03 after Bonferroni correction. SAS9.4 (Cary, NC, USA) was
