We evaluated PolyFun via simulations using real genotypes from 337,491 unrelated UK Biobank British samples27. We analyzed 10 3Mb loci on chromosome 1, each containing 1,468–27,784 imputed MAF≥0.001 SNPs (including short indels; Supplementary Table 2). We estimated prior causal probabilities using 18,212,157 genome-wide imputed MAF≥0.001 SNPs with INFO score≥0.6. We simulated traits with heritability equal to 25% and genome-wide proportion of causal SNPs equal to 0.5%, with each target locus including 10 causal SNPs jointly explaining heritability of 0.05%. We specified prior causal probabilities using the baseline-LF model25 with meta-analyzed functional enrichments from real data analyses (Supplementary Table 3). We generated summary statistics using N=320K samples. Further details are provided in the Methods section.
