We first evaluated the predictive performance of different polygenic prediction methods via simulations. We simulated individual-level genotypes of European (EUR), East Asian (EAS) and African (AFR) populations for HapMap3 variants with minor allele frequency (MAF) >1% in at least one of the three populations using HAPGEN237, with the 1KG Phase 3 samples as the reference panel. In our primary simulation setting, we randomly sampled 1% HapMap3 variants as causal variants, which in aggregation explained 50% of phenotypic variation in each population. We assumed that causal variants are shared across populations but allowed for varying effect sizes, which were sampled from a multivariate normal distribution with the cross-population genetic correlation (rg) set to 0.7. The simulation was repeated 20 times.
