We conducted a series of secondary simulations, by varying one parameter in the primary simulation at a time, to assess the generalizability of the above observations and the robustness of PRS-CSx across a wide range of genetic architectures, cross-population genetic overlaps and discovery GWAS sample sizes (Supplementary Note; Extended Data Figs. 1–7; Supplementary Tables 2–9). We concluded that, while the benefits of using a coupled prior varied with simulation designs and may be small in certain scenarios, PRS-CSx improved cross-population prediction accuracy relative to alternative methods across a vast majority of the simulation settings and was robust to model misspecification.
