it is possible that patterns of enrichment at extremely rare variants may be different from those inferred using this method (see Online Methods). Fifth, the method is limited by available functional data: if a trait is enriched in a cell type for which we have no data, we cannot detect the enrichment. Sixth, our method currently gives large standard errors when applied to very small categories (Supplementary Figure 8 and Supplementary Note). Last, though we have shown our method to be robust in a wide range of scenarios, we cannot rule out bias due to model misspecification caused by enrichment in an unidentified functional category as a possible source of bias; however our simulations show that our method gives nearly unbiased results even under very extreme scenarios of unmodeled functional categories (Figure 2).
