Figure 5  Enrichment Results for Three Selected Sets of Trait-Associated SNPs
(A) We examined the enrichment of 88 RA-associated variants with H3K4me3 in CD4+ T memory cells and in an aggregate of 118 different cell types and tissues. We assessed raw peaks (peak bodies) and summit regions (±100 bp from the summit). We observed a nominally significant enrichment in the aggregate of cell types and tissues (p = 0.044) and a pronounced enrichment within CD4+ T memory cells (p = 1.6 × 10−3). Stratified analysis indicated that the enrichment signal was driven by CD4+ T memory cells: the significance of the cell-type-aggregate enrichment decreased (p = 0.08) when we stratified on CD4+ T cells, but not vice versa (p = 2.7 × 10−3).
(B) We assessed the enrichment of 69 breast-cancer-associated variants with various histone marks (H3K4me3 and H3K4me1) in the 118 tissues and cell types. Breast-cancer-associated SNPs were highly enriched (p = 2 × 10−3) in summit regions of H3K4me1 peaks in vHMECs (left panel), but not in other cells, H3K4me3 summit regions (p > 0.4), or H3K4me1 peak bodies. The stratified enrichment analysis indicated that the enrichment of H3K4me1 summit regions in vHMECs was independent of the H3K4me1 summit regions in the aggregated cell types and tissues. The H3K4me1 enrichment in vHMECs within summit regions was maintained when we stratified on summit regions from other breast tissues and cell types (p < 3.6 × 10−3; right panel).
(C) Similarly, we assessed enrichment of 697 SNPs associated with height in DHSs from 217 different tissues. The height-associated SNPs showed the highest enrichment of DHSs in embryonic stem cells (p < 10−4) and CD3+ cells (p < 10−4) from cord blood (left panel). However, the CD3+ cell DHS enrichment diminished after stratification on embryonic stem cells (p = 0.08), whereas embryonic stem cells retained significance after stratification on CD3+ cells (p = 9.6 × 10−3; right panel).