We found genetic overlap between cannabis use disorder and several mental health phenotypes, respiratory illnesses, and infectious diseases in the BioVU biobank. The strongest association was with tobacco use disorder, but conditioning for loci associated with smoking initiation retained many of the pheWAS associations at significant levels, including anxiety, phobic and dissociative disorders, respiratory failure, and viral hepatitis. An even more stringent analysis that covaried for tobacco use disorder revealed independent associations with viral hepatitis, type 1 diabetes, respiratory measures, and pain, but not mental health. These associations could reflect genuine pleiotropy (eg, with risk-taking behaviours and injection drug use) or index putatively causal peripheral effects of cannabis. Cannabis use frequency in the UK Biobank was genetically correlated with cannabis use disorder as well, but, similarly to other psychiatric and behavioural traits,60 the PRS for cannabis use disorder explained only a small proportion of variance in cannabis use frequency (R2 0·04%).
