Some limitations of our study are noteworthy. First, comorbidities in the cross-disorder meta-analysis from which the PRS were derived, as well as in the target SAGE sample, may be subject to certain unmeasured confounds. For example, the PGC did not examine the extent of cocaine (or other substance) use in their sample population (Cross-Disorder Group of the Psychiatric Genomics Consortium, 2013), so our associations of SCZ PRS with severe cocaine dependence may be an artifact of increased cocaine use by people with schizophrenia (Serper et al., 1995), or of cocaine-induced psychosis resulting in a diagnosis of schizophrenia (Brady et al., 1991). Conversely, though severe psychopathology (i.e., AUT, BIP, SCZ) is likely to be uncommon in SAGE and unlikely to influence associations, more common psychopathologies (i.e., ADHD, MDD) were likely present. Therefore, associations with ADHD or MDD PRS may have been mediated by the actual expression of the disorder among SAGE participants (e.g., people with higher MDD PRS in SAGE develop MDD, which in turn is associated with substance use disorders). Though data on ADHD diagnosis in SAGE were unavailable, repeating
