We next used our tissue-specific epigenomic datasets to study the regulatory annotation enrichments of phenotype-associated variants from genome-wide association studies (GWAS) of diverse traits and disorders. Previous studies showed that disease-associated variants are enriched in specific regulatory chromatin states9, evolutionarily-conserved elements72, histone marks73, and accessible regions14. We expanded these analyses using the diversity of primary tissues surveyed by our epigenomic maps, applied to a compendium of disease-associated variants from the NHGRI GWAS catalog74. We intersected the set of variants identified in each curated study with peaks of H3K4me1, H3K4me3, H3K36me3, H3K27me3, and H3K9me3 across each of the 127 epigenomes, and H3K27ac, H3K9ac, and DNase when available (Extended Data 11-12, Table S6), and we searched for significant enrichment in their overlap relative to what would be expected given the NHGRI GWAS catalog as background (see Methods).
