Related to stratification, most PRS methods do not explicitly address recent admixture and none consider recently admixed individuals’ unique local mosaic of ancestry; further methods development is needed. Additionally, comparing PRS across environmentally stratified cohorts, such as in some biobanks with healthy volunteer effects versus disease study datasets or hospital-based cohorts, requires careful consideration of technical differences, collider bias, as well as variability in baseline health status among studies. It is also important to consider differences in definitions of clinical phenotypes and heterogeneity of sub-phenotypes among countries.
