There are a number of drawbacks to using EA GWAS for PRS construction in non-EA populations. Specifically, linkage disequilibrium (LD) patterns vary across populations, rendering different best available tag SNPs between populations; allele frequencies often differ across populations; and, at least for some traits, effect sizes differ between populations and allelic heterogeneity exists (The International HapMap Consortium, 2005; Musunuru et al., 2012). Admixed populations, such as Hispanics/Latinos, may have different genetic architecture and effect sizes at a genetic association region compared to an ancestral population due to gene-gene (epistasis) or gene-environment interactions, or because a causal variant is monomorphic in one ancestral population (Jain et al., 2017; Qi et al., 2017). Belsky et al. (2013) constructed a PRS for obesity based on EA GWAS results and found that its utility for an African American (AA) population was low, and much lower than that for an EA population. Martin et al. (2017) studied transferability of PRSs constructed based on single-ancestry GWASs to other ancestries, and demonstrated that scores inferred from EA GWASs may perform poorly in other ancestries. Others have recently
