loci with a synthetic functional annotation (see Methods) and either enriched or depleted causal variants within this annotation. We also compared our approach to fgwas [10] as it too is capable of inferring enrichment from summary data. Figure 3 demonstrates that both PAINTOR and fgwas are able to provide unbiased estimates of enrichment. However, we find that PAINTOR is more efficient than fgwas, and has a smaller variance attached to those estimates. We note that as causal variants become increasingly depleted from functional categories, fgwas tends to fail to converge (e.g. fgwas fails in nearly 21% of cases for simulations with 8-fold depletions). Finally, we assessed PAINTOR and fgwas for more realistic annotation data (i.e. contiguous segments in the genome) and find that both methods attain very similar results (see Figure S2).
