Polygenic Risk Scores (PRSs, see Table 1 for acronyms and shorthands) summarize the genetic component of a disease or quantitative (continuous) trait and are routinely used in public health genetics research for a wide range of applications, such as improving disease and trait prediction (Morrison et al., 2007); studying the shared genetic basis between traits (Raffield et al., 2017); increasing power by integrating over multiple variants rather than one variant at a time; and Mendelian Randomization studies (Voight et al., 2012; Vimaleswaran et al., 2013) in which a PRS associated with one trait is used as an instrumental variable in a causal analysis of the association of the trait with another outcome. PRSs are typically constructed as the weighted sum of risk alleles of single nucleotide polymorphisms (SNPs) associated with the trait of interest, where SNPs and weights are usually selected based on findings from published studies, such as Genome-Wide Association Studies (GWASs) (Qi et al., 2012). However, most GWASs to date have been performed in studies of individuals of exclusively or predominantly European genetic ancestry (EA). This poses a difficulty for PRS construction in non-EA populations.
