Following standard procedure, we trained a baseline LDSC model using the 52 non-cell-type specific functional categories (plus one category that includes all SNPs) and used the observed z-scores of HapMap3 SNPs for each trait. We tested cell-group enrichments over 10 pre-defined cell-group annotations22. The cell-group annotations are the result of aggregating 220 cell-type-specific annotations over 4 histone marks (H3K4me1, H3K4me3, H3K9ac, H3K27ac) and 100 well-defined cell types. To detect which specific epigenomes contribute to the group-level enrichment, we performed 220 tests over each individual annotation. Multiple testing was accounted for through Bonferroni correction within phenotype with 10 tests for the cell-group annotation enrichment analyses and 220 tests for the cell-specific enrichment analyses. As a complementary method to LDSC, we also applied a recently developed mixture model learning approach67, and report these results in Supplementary Figure 13.
