Fig. 5: Chromatin loops and regulatory elements in human retina support effect of colocalizing e/sQTLs on POAG risk. | Nature Communications

Fig. 5: Chromatin loops and regulatory elements in human retina support effect of colocalizing e/sQTLs on POAG risk.

From: Integrating genetic regulation and single-cell expression with GWAS prioritizes causal genes and cell types for glaucoma

Fig. 5

a Retina CREs (cyan) derived from epigenetic data overlapping e/sVariants that colocalized with POAG associations in the CDKN2A/B locus. The lead POAG variants from the cross-ancestry (blue line) and European subset (orange line) GWAS are shown in the top track, followed by their linkage disequilibrium (LD) proxy variants (r2 > 0.8) in the track below. The significantly colocalizing CDKN2B-AS1 sVariants in Pituitary, CDKN2A eVariants in Brain Cortex, and CDKN2B eVariants in Skeletal Muscle are represented by red lines, and the grey lines represent LD proxy variants to the colocalizing e/sVariants, which are also significant e/sQTLs (FDR < 0.05) for the corresponding gene and tissue. b Retina CREs (cyan) overlapping retina SLC2A12 eVariants that colocalized with the POAG cross-ancestry association. Tracks display the lead POAG cross-ancestry GWAS variant rs2811688 (orange) and its LD proxy variants (grey), followed by the significantly colocalizing SLC2A12 retina eVariants (red) with their LD proxy eVariants, which are also significant eQTLs at FDR < 0.05 (grey). The CRE overlaps the promoter of SLC2A12. c Retina chromatin loops from Hi-C (3D chromosome conformation capture) data, SEs (blue), and CREs (cyan) shown for the RERE POAG locus. Tracks display the lead POAG cross-ancestry GWAS variant rs172531 (orange) and its LD proxy variants (grey), followed by significantly colocalizing RERE eVariants in Nerve Tibial, RERE sVariants in Cell-Cultured Fibroblast cells, and RERE-AS1 eVariants in Adipose Subcutaneous (red), and their LD proxy variants that are also significant e/sQTLs (FDR < 0.05) for the corresponding gene and tissue (grey). Magenta loops have one foot that overlaps or is in LD with the POAG variant and colocalizing e/sQTLs. In all panels, LD proxy variants were computed at r2 > 0.8, TADs are represented as solid black lines, and the magenta heatmaps represent Hi-C physical contact maps. CRE Cis-regulatory element, SE Super-enhancer, TAD Topologically associating domain.

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