Secondary simulation studies using (1) the point-normal model with different total heritability (0.2 and 0.8); (2) a point-t model with different numbers of causal variants; and (3) a point-gamma model with different numbers of causal variants produced similar patterns of prediction accuracy (Supplementary Figs. 1–4; Supplementary Tables 2–5) and calibration properties (Supplementary Tables 8–11). Using the combined UK Biobank validation and testing data sets (N = 6000) as an in-sample LD reference panel in the point-normal simulations produced, in general, slightly higher prediction accuracy for methods making use of LD information (Supplementary Fig. 5; Supplementary Tables 6 and 12), suggesting that using a larger reference panel that better aligns with the LD structure of the target sample may increase predictive performance. However, as the improvement was marginal, it appears that the performance of PRS-CS(-auto) is not particularly sensitive to the LD reference panel, and 1KG can serve as a valid reference despite its relatively small sample size.
