The substantial comorbidity between psychiatric and substance use disorders is unequivocal (e.g., Swendsen et al., 2010; Hasin and Kilcoyne, 2012), but sources contributing to this covariation remain less well articulated. Complementing prior observations from latent genetic (e.g., Kendler et al., 2003) and candidate gene (e.g., Yoshimasu et al., 2015) studies, we report that PRS derived from the PGC cross-disorder meta-analysis (CROSS; Cross-Disorder Group of the Psychiatric Genomics Consortium, 2013) explained roughly 1% of the variance in general substance involvement (GENSUB) in our target sample enriched for substance use (SAGE; Bierut et al., 2010). This effect size is consistent with previously published cross-trait PRS analyses (e.g., Cross-Disorder Group of the Psychiatric Genomics Consortium, 2013; Krapohl et al., 2015), and, though not large enough to be informative on an individual level, nonetheless provides support for the hypothesized role of shared genetics in the lifetime co-occurrence of psychiatric and substance use disorders. PRS for individual psychiatric diagnoses (i.e., ADHD, BIP, MDD, and SCZ, but not AUT) were also significantly associated with specific substance involvement (i.e., alcohol, cannabis, cocaine, nicotine, and opioids), and are
