Tissue-specific activity of disease-associated regions

We tested the enrichment of SNPs from individual Genome-wide Association Studies (GWAS) for the gapped peak call sets for histone marks H3K4me1, H3K4me3, H3K36me3, H3K9me3, H3K27me3, H3K9ac, and H3K27ac as well as the DNase peak call set based on MACS2 in each reference epigenome where available. The SNPs used were curated into the NHGRI GWAS catalog (Welter et al. (2014)) and obtained through the UCSC Table Browser (Karolchik et al. (2004)) on September 12, 2014. We restricted the enrichment analysis to chr1-22 and chrX. We defined a study to be a unique combination of annotated trait and pubMedID. To reduce dependencies between pairs of SNPs assigned to the same study, we pruned SNPs such that no two SNPs were within 1MB of each other on the same chromosome. The pruning procedure considered each SNP in ranked order of p-value with the the most significant coming first, and we retained a SNP if there was no already retained SNP on the same chromosome within 1MB. We computed hypergeometric p-values for the enrichment of each pruned set of SNPs overlapping peak calls against the pruned GWAS catalog as the background. We estimated separately for each mark a mapping from a p-value to a false discovery rate across tests for all study and reference epigenome combinations by generating 100 randomized versions of the pruned GWAS catalogs shuffling which SNPs were assigned to which study and computing the average fraction of reference epigenomestudy combinations that reached that level of significance (in a continuous mapping of p-values to FDR) using randomized catalogs divided by the number based on the actual GWAS catalog.