Though not included in PGC cross-disorder analyses, evidence suggests that substance use disorders are heritable (h2 = 40–70%; Kendler et al., 2012), frequently co-occur (Kendler et al., 2007), and are highly comorbid with other forms of psychopathology (Swendsen et al., 2010; Hasin and Kilcoyne, 2012). Such comorbidity is associated with increased severity and poorer outcomes for all disorders (Lehman et al., 1993), though it is unclear whether this relationship is causal (e.g., psychopathology leading to self-medication with substances, or substance use leading to psychopathology through dysregulation of neurotransmitter systems) or the result of overlapping risk factors (e.g., shared genetics and/or environment; Agrawal and Lynskey, 2014). Despite this, few studies have explored the role of shared genetic influence on comorbidity between substance use disorders and other psychiatric illnesses. Family studies remain equivocal about the co-transmission of substance use disorders and severe mental illness (e.g., schizophrenia and bipolar disorder: Kendler et al., 1993; Winokur et al., 1995); however, twin studies support the role of shared genetic liability for more common forms of psychopathology (Kendler et al., 2003). Collectively, these data hint at the possibility that genetic factors contributing to a range of psychopathologies also contribute to a general risk for substance involvement.
