Language
English
Publication Date
1-9-2024
Journal
Nature Communications
DOI
10.1038/s41467-023-44380-y
PMID
38195602
PMCID
PMC10776627
PubMedCentral® Posted Date
1-9-2024
PubMedCentral® Full Text Version
Post-print
Abstract
Primary open-angle glaucoma (POAG), characterized by retinal ganglion cell death, is a leading cause of irreversible blindness worldwide. However, its molecular and cellular causes are not well understood. Elevated intraocular pressure (IOP) is a major risk factor, but many patients have normal IOP. Colocalization and Mendelian randomization analysis of >240 POAG and IOP genome-wide association study (GWAS) loci and overlapping expression and splicing quantitative trait loci (e/sQTLs) in 49 GTEx tissues and retina prioritizes causal genes for 60% of loci. These genes are enriched in pathways implicated in extracellular matrix organization, cell adhesion, and vascular development. Analysis of single-nucleus RNA-seq of glaucoma-relevant eye tissues reveals that the POAG and IOP colocalizing genes and genome-wide associations are enriched in specific cell types in the aqueous outflow pathways, retina, optic nerve head, peripapillary sclera, and choroid. This study nominates IOP-dependent and independent regulatory mechanisms, genes, and cell types that may contribute to POAG pathogenesis.
Keywords
Humans, Genome-Wide Association Study, Glaucoma, Open-Angle, Gene Expression Regulation, Causality, Glaucoma, Functional genomics, Statistical methods, Optic nerve diseases
Published Open-Access
yes
Recommended Citation
Hamel, Andrew R; Yan, Wenjun; Rouhana, John M; et al., "Integrating Genetic Regulation and Single-Cell Expression With Gwas Prioritizes Causal Genes and Cell Types for Glaucoma" (2024). Faculty and Staff Publications. 4360.
https://digitalcommons.library.tmc.edu/baylor_docs/4360
Included in
Endocrinology, Diabetes, and Metabolism Commons, Medical Sciences Commons, Ophthalmology Commons, Optometry Commons