age of first cannabis use35. The relationship these latter two traits bear to CUD is not entirely clear: these traits would appear to bear strong relationships to environmental exposures, drug availability and personality traits such as sensation seeking, as opposed to the transition from use to dependence. Larger studies directly relevant to CUD have shown association implicating CHRNA2 (2387 cases, 48,985 controls)36 and to several loci (e.g., forkhead box P2 (FOXP2)) including a confirmation of CHRNA2 effects in a recent Psychiatric Genomics Consortium (PGC; Box 2) meta-analysis37. The latter study, which included 20,916 cases and >300,000 controls, identified two loci, and showed partial genetic overlap between CUD and cannabis use (rg=0.50), generally consistent with the differences observed between quantity/frequency versus dependence measures of alcohol use12–14. Thus, the situation with CUD is illustrative of illegal SUDs in general: lower prevalence than alcohol and nicotine use, fewer available samples to study, and reduced gene discovery that is seen mostly in populations of European descent.
