The present study conducted a set of genetically informed analyses to investigate the nature of the association between psychotic disorders and cannabis phenotypes. We observed differences in the genetic architectures of SCZ, BIP, LCU and CUD. We found evidence of genetic overlap between each psychotic-cannabis phenotype pair at the genome-wide, regional, and locus levels. A group of shared loci, ranging from 3 to 27, with mixed effect directions was identified for each phenotype pair. Putative causal relationships were tested using MR, revealing evidence for some bidirectional causal associations. Additionally, combining the PGSs for cannabis phenotypes and psychotic disorders improved distinguishing SCZ and BIP patients from healthy participants. Overall, these findings suggest a shared genetic component underlying the phenotypic link between psychotic disorders and cannabis phenotypes with implications for guiding clinical practice and public policy.
