Hamel AR, Yan W, Rouhana JM, Monovarfeshani A, Jiang X, Mehta PA, Advani J, Luo Y, Liang Q, Rajasundaram S, Shrivastava A, Duchinski K, Mantena S, Wang J, van Zyl T, Pasquale LR, Swaroop A, Gharahkhani P, Khawaja AP, MacGregor S, Hewitt AW, Schuster AK, Viswanathan AC, Lotery AJ, Cree AJ, Pang CP, Brandl C, Klaver CC, Hayward C, Khor CC, Cheng CY, Hammond CJ, van Duijn C, Mackey DA, Stefansson E, Vithana EN, Pasutto F, Jonansson F, Thorleifsson G, Koh J, Wilson JF, Craig JE, Vergroesen JE, Fingert JH, Jonas JB, Stefánsson K, Burdon KP, Chen LJ, Kass M, Jansonius NM, Pfeiffer N, Polašek O, Foster PJ, Mitchell P, Hysi PG, Wojciechowski R, Driessen SJ, Tompson SW, Young TL, Wong TY, Aung T, Thorsteinsdottir U, de Vries VA, Ramdas WD, Wang YX, Chen R, Vitart V, Sanes JR, Wiggs JL, Segrè AV (2024)
Publication Type: Journal article
Publication year: 2024
Book Volume: 15
Article Number: 396
Journal Issue: 1
DOI: 10.1038/s41467-023-44380-y
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.
APA:
Hamel, A.R., Yan, W., Rouhana, J.M., Monovarfeshani, A., Jiang, X., Mehta, P.A.,... Segrè, A.V. (2024). Integrating genetic regulation and single-cell expression with GWAS prioritizes causal genes and cell types for glaucoma. Nature Communications, 15(1). https://doi.org/10.1038/s41467-023-44380-y
MLA:
Hamel, Andrew R., et al. "Integrating genetic regulation and single-cell expression with GWAS prioritizes causal genes and cell types for glaucoma." Nature Communications 15.1 (2024).
BibTeX: Download