Integration of epigenetic annotations and GWAS shows enrichment for disease heritability in retina and brain microglia. (A) MAGMA enrichment analysis of open chromatin data. Bar plots display the mean strength of association (–log10 P-values) for MAGMA enrichment in retina and brain cell types, highlighting significant enrichment in retina and brain microglia for AMD–GWAS variants. (B) MAGMA enrichment analysis of AD–GWAS variants in open chromatin data across retina and brain cell types, showing significant enrichment specifically in retina and brain microglia. (C) Heritability enrichment estimates from retina and brain annotations for AMD–GWAS variants using S-LDSC. (D) Enrichment estimates with S-LDSC for epigenetic annotations from retina and brain cell types for AD. In all four plots, the dashed line marks the P-value significance for individual annotations, and asterisks represent the significant at an FDR <5%. (E,F) GARFIELD enrichment analysis of open chromatin data for AMD–GWAS (E) and AD–GWAS (F) for retina and brain cell types. Radial lines show odds ratio (OR) values at five GWAS P-value thresholds (T) for ATAC-seq peaks from retina and brain microglia cell types. Colored dots in the inner ring of the outer circle show where GARFIELD enrichment is significant, with stronger significance closer to the center (from T < 10−5 to T < 10−8). The dot's color represents a specific cell type. (G,H) The bar plot shows enrichment for AMD-associated (G) and AD-associated (H) variants in ATAC-seq data from ENCODE and Roadmap Epigenomics data sets across different tissues. ORs for enrichment are shown for variants at GWAS threshold of P < 1 × 10−8 after multiple-testing correction for the number of effective annotations. The dashed lines represent the P-value significance threshold for enrichment. (RGC) Retinal ganglion cell, (Retina-specific MG) DARs identified between in retina microglia compared with brain microglia, and (Brain-specific MG) DARs identified between in brain microglia compared with retina microglia.
