Fig. 8: Cell type enrichment of e/sQTL-mapped genes to POAG, IOP and related trait loci in retina, optic nerve head and surrounding posterior tissues.

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, IOP, physician-defined vertical-cup-to-disc ratio (VCDR) or machine learning-defined VCDR (VCDR ML) GWAS, using ECLIPSER (one-sided), shown for all cell types in retina (a) and optic nerve head (ONH), optic nerve (ON), peripapillary sclera, sclera, and choroid (b). Traits (rows) and cell types (columns) were clustered based on hierarchical clustering of Euclidean distance between 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). Colored boxes highlight trait-specific enriched cell types. c Cell type-specificity fold-enrichment (x-axis) in ONH and surrounding tissue cell types ranked in descending order for the POAG cross-ancestry GWAS locus set (No. loci=79). Points: fold-enrichment estimates from ECLIPSER. Error bars: 95% confidence intervals. Exact p-values (one-sided) are provided in Supplementary Data 35. d Differential expression (log₂(Fold-change)) in astrocytes (6-Astro) in ONH compared to all other cell types in the posterior tissues is shown for the e/sGenes driving the POAG enrichment signal in astrocytes. 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 Expression profile of e/sGenes driving the POAG cross-ancestry enrichment signal in astrocytes (red box) shown across all ONH and surrounding tissue cell types. Colorbar represents gene expression z-scores computed by comparing each gene’s average expression in a given cell type to its average expression across all types divided by the standard deviation of all cell type expression averages. Bubble size is proportional to percentage of cells expressing the gene (log(TPK + 1) > 1). f LocusCompare plot of -log₁₀(P-value) of POAG cross-ancestry GWAS meta-analysis relative to -log₁₀(P-value) of DGKG retina eQTL, which significantly colocalized with POAG locus rs56233426 (chr3_186411027_G_A). Points are color-coded based on LD (r²) relative to the eVariant with highest eCAVIAR colocalization posterior probability (CLPP = 0.93). Cell type abbreviations are described in Supplementary Data 35.