In independent models, cannabis use ever (0: never, 1: ever use) and DSM-5 CUD symptom counts (0–11 symptoms, log-transformed) were regressed using Poisson models on cannabis ever use PRS from the Pasman et al. study9. Models were adjusted for ancestral PCs (PC1–PC3), age (range: 12–91 years; mean = 36.77, SD: 14.83), birth cohort (dummy variables representing birth years prior to 1930, 1930–1949, 1950–1969, and 1970 and after), and sex (0 = male, 1 = female), given prior evidence that cannabis use and problems differ across these groups46. In addition, genotype array was used as a covariate in all analyses since different platforms were used across the sample (detailed above). In addition, we accounted for the nested nature of the family-based sample in all regression analyses using hierarchical multi-level modeling. A Bonferroni correction for multiple testing, adjusting for two cannabis-related outcomes and nine PRS thresholds was applied to all findings, requiring a p value < 0.003 to meet criteria for statistical significance. Cannabis use and CUD were moderately correlated (r2: 0.40, p < 0.001); PRS across varying thresholds were only modestly
