We downloaded narrow peaks from the Roadmap Epigenomics consortium for DNase hypersensitivity and five activating histone marks: H3K27ac, H3K4me3, H3K4me1, H3K9ac, and H3K36me3 (see URLs). Each of these six features was present in a subset of the 88 primary cell types/tissues, for a total of 397 cell-type-/tissue-specific annotations. We also analyzed peaks called using Homer from EN-TEx, a subgroup of the ENCODE project, for four activating histone marks: H3K27ac, H3K4m3, H3K4me1, and H3K36me3. Each of these four features was present in a subset of 27 tissues that were also included in the GTEx data set, for a total of 93 cell-type-/tissue-specific annotations. For each of these two datasets, of each of the annotations, we tested for enrichment by adding the annotation to the baseline model (see Table S1), together with the union of cell-type-specific annotations within each mark and the average of cell-type-specific annotations within each mark. A positive regression coefficient for a tissue-/cell-type-specific annotation represents a positive contribution of the annotation to per-SNP heritability, conditional on the other annotations. We again computed a P-value to test whether the regression coefficient was positive.
