In particular, PRS accuracy is also a function of recent human demographic history, such that a greater proportion of phenotypic variance is explainable in target populations that are genetically more similar to the population studied in the discovery GWAS. Stated another way, with increasing genetic “distance” between the discovery and target datasets, there is often attenuation of polygenic predictive value. Furthermore, because most participants in large GWAS have been broadly European (Figure 1), most PRS currently perform best in target samples of European ancestries, with markedly worse performance in other populations, especially in individuals of African descent (Duncan et al., 2018; Martin et al., 2019).
