In our opinion, current PRS are not clinically actionable, even though some studies have proposed to have identified marker sets (using other related approaches) that can be diagnostically implemented (Skafidas et al., 2014, Robinson et al., 2014, Belgard et al., 2014). Pleiotropic effects of PRS are evident from Figure 2 and Tables 1–6. How this overgeneralized liability can be harnessed to refine treatment currently remains unclear. At present, the utility of PRS might lie, not as harbingers of future diagnosis but as indicators of vulnerability, which may be modified by a variety of other mitigating or exacerbating influences (e.g., environment, modifier loci). For example, using traditional PRS analyses, SCZ PRS can account for up to 18% of the variance in liability to schizophrenia in an independent dataset with the upper decile being associated with an OR of 20. Such information may be leveraged to identify individuals at risk. While this likely would not currently impact the immediate treatment that one would receive, it would be intriguing to evaluate whether those most genomically vulnerable respond better or worse to early interventions,
