PRS, but also have their own challenges (Bogdan et al., 2017). Along these lines, PRS are not currently amenable to direct translational work in nonhuman animals, though multiplex CRISPR/Cas9 approaches are beginning to be employed (Cong et al., 2013, Wang et al., 2013), which may ultimately be used to model polygenic variability. Third, while PRS are more predictive than single common polymorphisms, they are not currently predictive of substantial variance, even in the same phenotype as originally probed (with the exception of schizophrenia; see Technical Considerations). As a result, for adequate power, they still require relatively large samples (>300 for optimistic estimates of cross trait assocaitions using traditional PRS). Fourth, PRS assume additivity. While this assumption has support (Hill et al., 2008), evidence of epistasis is also present (Gibert et al., 2017, Mitra et al., 2017, Hemani et al., 2014).
