Retinal ganglion cell-specific genetic regulation in primary open-angle glaucoma

Maciej Daniszewski, Anne Senabouth, Helena H. Liang, Xikun Han, Grace E. Lidgerwood, Damián Hernández, Priyadharshini Sivakumaran, Jordan E. Clarke, Shiang Y. Lim, Jarmon G. Lees, Louise Rooney, Lerna Gulluyan, Emmanuelle Souzeau, Stuart L. Graham, Chia Ling Chan, Uyen Nguyen, Nona Farbehi, Vikkitharan Gnanasambandapillai, Rachael A. McCloy, Linda ClarkeLisa S. Kearns, David A. Mackey, Jamie E. Craig, Stuart MacGregor, Joseph E. Powell, Alice Pébay, Alex W. Hewitt

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


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.
Original languageEnglish
Article number100142
JournalCell Genomics
Issue number6
Publication statusPublished - 8 Jun 2022


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