SCZ PRS were associated with involvement across all substances tested, but only associations with non-problem cannabis use and severe cocaine dependence persisted upon inclusion of GENSUB. Notably, both substances have been previously implicated in the etiology of psychotic illness. Cocaine use is common among individuals with SCZ (Shaner et al., 1995), and several neurobiological models have implicated shared disruptions in dopaminergic signaling as a common etiological explanation for this comorbidity (e.g., Volkow, 2009). Adolescent exposure to cannabis has long been posited as either a directly causal (Arseneault et al., 2004) or moderating (Henquet et al., 2008) factor in the etiology of psychosis, but recent research has suggested that associations may be due in part to shared genetic factors (Power et al., 2014; Pagliaccio et al., 2015). For example, complementing our current results, a prior study reported a significant association between SCZ PRS and lifetime and frequency of cannabis use (Power et al., 2014). Taken together, these results suggest a specific genetic etiological link between schizophrenia, cannabis use, and cocaine dependence.
