Fig. 2: Performance comparison of alternative methods on simulated data generated with different sample sizes and genetic architectures under strong negative selection and fixed common-SNP heritability.

Data are simulated for continuous phenotype under a strong negative selection model and three different degrees of polygenicity (top panel: \({p}_{{causal}}=0.01\), middle panel: \({p}_{{causal}}=0.001\), and bottom panel: \({p}_{{causal}}=5\times {10}^{-4}\)). Common SNP heritability is fixed at 0.4 across all populations, and the correlations in effect sizes for share SNPs between all pairs of populations is fixed at 0.8. The sample sizes for GWAS training data are assumed to be a n = 15,000, and b n = 80,000 for the four non-EUR target populations; and is fixed at n = 100,000 for the EUR population. PRS generated from all methods are tuned in n = 10,000 samples, and then tested in n = 10,000 independent samples in each target population. The PRS-CSx package is restricted to SNPs from HM3, whereas other alternative methods use SNPs from either HM3 or MEGA. Bars in the figure show the performance of R² for each method in each dataset. Colors are described on the right side of the figure. Source data are provided in Supplementary Data 1.