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 most consistent with a multifactorial model,44,45 wherein polygenic risk for schizophrenia combines additively with environmental risk factors, including early and heavy cannabis use, to increase an individual’s vulnerability to unusual cannabis-related experiences. Relatedly, while we found that CUD severity and polygenic risk for schizophrenia were both associated with the endorsement of a greater number of cannabis-related experiences, the schizophrenia PRS and CUD severity were not related, suggesting that these factors independently contribute to the risk of cannabis-related experiences in this sample.
