Figure 2.

PRS construction approaches and performance in admixed individuals

Using significant variants from an African ancestry GWAS with population-specific weights results in less disparity in PRS accuracy across populations. PRSs were constructed using variants and weights selected from either a European or African population (10,000 cases, 10,000 controls each) or a fixed-effects meta-analysis of both. An additional local ancestry-specific method was used for PRS weighting. Performance, measured as the Pearson’s correlation between the true and GWAS estimated risk score, is shown across 50 simulations. Simulations assume 1,000 causal variants and a heritability of 0.5 to compute the true genetic risk. A p value of 0.01 and LD r² cutoff of 0.2 was used to select variants for the estimated risk scores.