The genetic relationship between cannabis use disorder, cannabis use and psychiatric disorders

Increasing prevalence of cannabis use and cannabis use disorder (CanUD) may increase risk for psychiatric disorders. We evaluated the relationships between these cannabis traits and a range of psychiatric traits, running global and local genetic correlations, genomic structural equation modeling, colocalization analyses and Mendelian randomization analyses for causality. Global genetic analyses identified significantly different correlations between CanUD and cannabis use. A variant in strong linkage disequilibrium to one regulating CHRNA2 was significantly shared by CanUD and schizophrenia in colocalization analysis and included in a significant region in local genetic correlations between these traits. A three-factor model from genomic structural equation modeling showed that CanUD and cannabis use partially map together onto a factor with major depressive disorder and ADHD. In terms of causality, CanUD showed bidirectional causal relationships with most tested psychiatric disorders, differently from cannabis use. Increasing use of cannabis can increase rates of psychiatric disorders over time, especially in individuals who progress from cannabis use to CanUD.