Fig. 6: Cell type enrichment of e/sQTL-mapped genes to POAG, IOP and related trait GWAS loci in the ocular anterior segment. | Nature Communications

Fig. 6: Cell type enrichment of e/sQTL-mapped genes to POAG, IOP and related trait GWAS loci in the ocular anterior segment.

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

Fig. 6

a Significance (circle size, -log10 (P-value)) and fold-enrichment (circle color) of the cell type specificity of e/sGene mapped-GWAS locus sets for POAG cross-ancestry, POAG European (EUR) subset, intraocular pressure (IOP), central cornea thickness, corneal hysteresis, physician-defined vertical-cup-to-disc ratio (VCDR), and machine learning-defined VCDR (VCDR ML), and as positive controls, eye color and cataract, using ECLIPSER (one-sided test), shown for 39 cell types in six ocular anterior segment tissues. Traits (rows) and cell types (columns) were clustered based on hierarchical clustering of Euclidean distance between the cell type-specificity enrichment scores of GWAS locus sets. Red rings: experiment-wide significant (Benjamini-Hochberg (BH) FDR < 0.1). Yellow rings: tissue-wide significant (BH FDR < 0.1). Grey rings: nominal significant (P < 0.05). b, d Cell type specificity fold-enrichment (x-axis) in the anterior segment cell types ranked in descending order for e/sQTL-mapped genes to GWAS loci of the POAG European subset (No. loci (N) = 37) (b) and POAG cross-ancestry (N = 79) (d). Points: fold-enrichment estimates from ECLIPSER. Error bars: 95% confidence intervals. Red: tissue-wide significant (BH FDR < 0.1). Grey: nominal significant (P < 0.05). Blue: non-significant (P ≥ 0.05). The exact p-values (one-sided) for the fold-enrichment of all cell types and GWAS are provided in Supplementary Data 35. c Differential gene expression (log2(Fold-change), y axis) in the most strongly enriched cell type compared to all other cell types is shown for the set of genes (x axis) driving the enrichment signal of the POAG European GWAS loci in ciliary fibroblasts. The horizontal dashed line represents log2(Fold-change) of 0.375 (FC = 1.3) and FDR < 0.1 used as the cell type-specificity enrichment cutoff. e Heatmap of fraction of genes that overlap between the e/sGenes driving the enrichment signal for top ranked cell types (P < 0.05) in the anterior segment for POAG cross-ancestry GWAS loci. Numbers refer to fraction of e/sGenes driving the cell type enrichment on each row that overlaps with the genes driving the cell type enrichment on the corresponding column. Hierarchical clustering was performed on both rows and columns using Euclidean distance between fractions. Cell type abbreviations are described in Supplementary Data 35.

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