Some previous cross-sectional studies have linked differences in grey matter volume with cannabis use and dependence;61 however, a large mega-analysis did not find reductions in global or regional volumes in cannabis-dependent adults compared with controls.62 In our study, the association between PRS for cannabis use disorder and white matter volume persisted in the subset of children who were not exposed to any substance, including prenatally. This finding suggests that polygenic liability for cannabis use disorder might index differences in white matter volume in the developing brain, independently of the onset of substance use behaviours. Still, the association between PRS for cannabis use disorder and white matter was small (R2 0·15–0·18%), and additional studies are needed to confirm this association.
