Substance use and substance use disorders are partially distinct, and although excessive substance use is a necessary component of it, substance use disorders relate to psychological and physiological impairment related to excess use and aspects of loss of control over the behavior. Consistent with our findings for alcohol, accumulating evidence suggests that genetic liability to other psychiatric traits (e.g., schizophrenia) is strongly correlated with liability to substance use disorders (e.g., AUD) but not substance use (e.g., alcohol consumption). Genetic liability to alcohol use has also been correlated with liability to psychiatric traits (e.g., major depression) in opposite directions depending on level of involvement (Kranzler et al., 2019). However, we did not find similar elevations in rgs when contrasting ever smoking and ND, nor comparing cannabis initiation to CUD. It is possible that the lack of genetic overlap between AN and ND, as well as AN and CUD, is related to the relatively modest sample size of those discovery GWAS. A similar non-significant rg was noted for AUD when the Walters et al. (2018) alcohol dependence GWAS was used as the
