Fourth, while our PRS approach yielded evidence that shared common genetic architecture contributes to comorbidity between psychopathology and substance involvement, it does not provide insight into specific biological (e.g., reward-related neural responsiveness, epigenetically medicated changes in gene expression), psychological (e.g., anhedonia, impulsivity), and/or experiential (e.g., early life stress, peer group) mechanisms through which this risk is manifest (e.g., Olfson et al., 2014; Peña-Oliver et al., 2016; Ron and Barak, 2016). Compelling evidence suggests that psychopathology and substance involvement share overlapping neural systems (e.g., Buckholtz and Meyer-Lindenberg, 2012), molecular pathways (e.g., Ng et al., 2013), and environmental exposures (e.g., Kristjansson et al., 2016). Future PRS research probing biological systems and psychological traits common to both psychiatric and substance use disorders (e.g., Lancaster et al., 2016; Peña-Oliver et al., 2016) and incorporating environmental/experiential measures (e.g., French et al., 2015), alongside genomewide efforts to partition heritability into specific pathways and functional categories (e.g., Lee et al., 2012; Finucane et al., 2015), will further our understanding of the mechanisms underlying this comorbidity (Bogdan et al., 2016).
