In our simulations, population-specific weighting of PRS SNPs discovered in European ancestry populations improved PRS accuracy; however, the disparity between performance in European ancestry individuals versus African and admixed ancestry individuals remained large. We aimed to explore the potential improvements in PRS that could be gained by including variants discovered in large, adequately powered African ancestry cohorts. Following clumping and thresholding of significant variants using LD and summary statistics from the simulated African populations, an average of 5,269 (range = [4,462–6,071]) variants were included in the PRS (Table 1), reflective of the greater genetic diversity and decreased LD compared to Europeans.23 In contrast, when constructing a PRS using the same LD and p value criteria applied to a fixed-effects meta-analysis of European and African ancestry, an average of only 92 (range = [38–197]) variants were included in the PRS. This substantially smaller number was a result of few variants being statistically significant in both populations. Of the total number of variants included from the European GWAS, African ancestry GWAS, and fixed-effects meta-analysis, only 1.15%, 0.54%, and 15.0% on average were
