distributed across the genome), per-SNP heritability estimates would be nearly constant and therefore results in similar performance to LDpred. We have performed an additional simulation to demonstrate this using WTCCC genotype data with ~15K individuals and ~330K variants. We randomly divided the genome into two parts (two annotations) and uniformly selected causal SNPs. Then the traits were simulated in a similar way as other simulations in this paper. We estimated per-SNP heritability using LDSC in the two annotation categories, respectively. We ran the procedure for 100 times and the distributions of estimated per-SNP heritability in both regions are summarized in the figure below (the dashed line denotes the true per-SNP heritability, added as S4 Fig in the manuscript), which indicates that the per-SNP heritability estimates are uniform across the genome under constant enrichment. Therefore, AnnoPred would be mathematically equivalent with LDpred with enrichment is constant. We downloaded python code for PRSP+T and LDpred from Github (https://github.com/bvilhjal/ldpred). All the tuning parameters were tuned through cross-validation as we did for AnnoPred. Besides all these PRSs, we also compared AnnoPred with a evaluating method used in [5], which uses 1E-1, 1E-2,…, 1E-5 as p-value threshold to select SNPs and report the accuracy for
