interactions. It is worth noting that the strongest interaction effect observed, which suggested that polygenic liability for schizophrenia has a greater effect on risk for any cannabis-related experiences in individuals with a CUD diagnosis, was actually stronger in the model that controlled for all covariate-by-PRS and covariate-by-CUD interactions37 compared to the model without these terms (beta = 0.43, SE = 0.14, P = .003 vs beta = 0.29, SE = 0.12, P = .01). Our primary interaction models were on the multiplicative scale, a test of whether the combined effect of the PRS and moderator differs from the product of their individual effects. However, in light of these null findings, we subsequently tested interactions on the additive scale, which tests whether the combined effect of the PRS and moderator differs from the sum of their individual effects. Some have argued that departures from additivity may be more meaningful biologically than multiplicative models.42,43 Supporting this theory, several of the interactions were stronger in the additive models (eg, PRS-by-age at first use predicting cognitive difficulties P = .004, PRS-by-CUD predicting cognitive difficulties P = .0011), though none of the interaction effects passed our statistical significance threshold (α = 9.8e−4). Our findings are
