The widespread use of PRS to represent generalizable polygenic disorder risk is beginning to provide tractable information about how polygenic liability leads to psychiatric expression as well as the structure of and mechanisms underlying psychiatric comorbidity. At present PRS have the most promise to improve our understanding of putative mechanisms of genetic liability. In this context, it is important to conceptualize such measures as indicators of vulnerability, rather than harbingers of future diagnosis. In fact, any current genetic prediction panel for psychiatric disorders that relies on common variation should be evaluated with considerable rigor for its purported clinical utility. Nonetheless, a unique strength to this approach is that PRS may be applied to large general population samples studying deeply phenotyped constructs, extending the range of psychiatric genetics research. Further, it will be important to consider that effect sizes are small and currently can reasonably be expected to account for only 0.01–3% of variance in related phenotypes when designing studies. In this context, it is critical for adequately powered research to be conducted so that false positive and false negative findings do not misguide research efforts.
