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Retinal ganglion cell-specific genetic regulation in primary open-angle glaucoma
Citation
Daniszewski, M and Senabouth, A and Liang, HH and Han, X and Lidgerwood, GE and Hernandez, D and Sivakumaran, P and Clarke, JE and Lim, SY and Lees, JG and Rooney, L and Gulluyan, L and Souzeau, E and Graham, SL and Chan, CL and Nguyen, U and Farbehi, N and Gnanasambandapillai, V and McCloy, RA and Clarke, L and Kearns, LS and Mackey, DA and Craig, JE and MacGregor, S and Powell, JE and Pebay, A and Hewit, AW, Retinal ganglion cell-specific genetic regulation in primary open-angle glaucoma, Cell Genomics, 2, (6) Article 100142. ISSN 2666-979X (2022) [Refereed Article]
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DOI: doi:10.1016/j.xgen.2022.100142
Abstract
To assess the transcriptomic profile of disease-specific cell populations, fibroblasts from patients with primary open-angle glaucoma (POAG) were reprogrammed into induced pluripotent stem cells (iPSCs) before being differentiated into retinal organoids and compared with those from healthy individuals. We performed single-cell RNA sequencing of a total of 247,520 cells and identified cluster-specific molecular signatures. Comparing the gene expression profile between cases and controls, we identified novel genetic associations for this blinding disease. Expression quantitative trait mapping identified a total of 4,443 significant loci across all cell types, 312 of which are specific to the retinal ganglion cell subpopulations, which ultimately degenerate in POAG. Transcriptome-wide association analysis identified genes at loci previously associated with POAG, and analysis, conditional on disease status, implicated 97 statistically significant retinal ganglion cell-specific expression quantitative trait loci. This work highlights the power of large-scale iPSC studies to uncover context-specific profiles for a genetically complex disease.
Item Details
| Item Type: | Refereed Article |
|---|---|
| Keywords: | eQTL; glaucoma; human induced pluripotent stem cells; retinal ganglion cells; retinal organoids; single-cell RNA sequencing; transcriptomics. |
| Research Division: | Biomedical and Clinical Sciences |
| Research Group: | Ophthalmology and optometry |
| Research Field: | Optical technology |
| Objective Division: | Health |
| Objective Group: | Clinical health |
| Objective Field: | Treatment of human diseases and conditions |
| UTAS Author: | Hewit, AW (Professor Alex Hewitt) |
| ID Code: | 155571 |
| Year Published: | 2022 |
| Deposited By: | Menzies Institute for Medical Research |
| Deposited On: | 2023-03-01 |
| Last Modified: | 2023-03-01 |
| Downloads: | 0 |
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