Figure. 3. Overlaps of VISION cCREs with other catalogs and enrichment for variants associated with blood cell traits.

(A) Venn diagram showing intersections of human VISION cCREs with a combined superset of elements associated with nuclear structure (CTCF OSs, loop anchors, and TAD boundaries) and with a combined superset of DNA intervals associated with cis-regulatory elements (CREs), including TSSs, CpG islands, peaks from a massively parallel promoter and enhancer assay, and enhancers predicted from enhancer RNAs, peaks of binding by EP300, and histone modifications in erythroblasts (see Supplemental Material, Supplemental Fig. S9, and Supplemental Table S5). (B) The proportions of cCREs and randomly selected, matched sets of intervals in the overlap categories are compared in the bar graph. For the random sets, the bar shows the mean, and the dots show the values for each of ten random sets. (C) The UpSet plot provides a higher resolution view of intersections of VISION cCREs with the four groups of CRE-related elements, specifically enhancer-related (Enh), transcription start sites (TSS), Survey of Regulatory Elements (SuRE), and CpG islands (CpG). The enrichment for the cCRE overlaps compared to those in randomly selected, matched sets of intervals are shown in the boxplots below each overlap subset, with dots for the enrichment relative to individual random sets. (D) Overlaps and enrichments of VISION cCREs for three sets of structure-related elements, specifically CTCF OSs (CT), loop anchors (LA), and TAD boundary elements. (E) Overlaps of VISION cCREs with two sets of experimentally determined blood cell cCREs. (F) Enrichment of SNPs associated with blood cell traits from UK Biobank in VISION cCREs. Results of the sLDSC analysis of all cCREs are plotted with enrichment of the cCRE annotation in heritability of each trait on the x-axis, and the significance of the enrichment on the y-axis. The analysis covers 292 unique traits with GWAS results from both males and females and 3 traits with results only from males. The vertical dotted line indicates an enrichment of 1, and the horizontal dotted line delineates the 5% FDR significance threshold. Points and labels in red represent traits for which there was significant enrichment of SNPs associated with the VISION cCREs. Traits with a negative enrichment were assigned an arbitrary enrichment of 0.1 for plotting and appear as the column of points at the bottom left of the plot. The shape of the point indicates the sex in which the GWAS analysis was performed for each trait.