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

• DOI: 10.1016/j.xgen.2022.100142
• Publication Date: 2022-06-08T17:13:52Z
• Authors: Maciej Daniszewski; Anne Senabouth; Helena H. Liang; Xikun Han; Grace E. Lidgerwood; Damián Hernández; Priyadharshini Si...; 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 Gnana...; Rachael A. McCloy; Linda Clarke; Lisa S. Kearns; David A. Mackey; Jamie E. Craig; Stuart MacGregor; Joseph E. Powell; Alice Pébay; Alex W. Hewitt
• Keywords: Candidate gene; Genome-wide Association Study

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 retinal organoids and compared those healthy individuals. We performed single-cell RNA sequencing a total 247,520 identified cluster-specific molecular signatures. Comparing gene expression between cases controls, we novel genetic associations for this blinding disease. Expression quantitative trait mapping 4,443 significant loci across all types, 312 which are specific to ganglion subpopulations, ultimately degenerate in POAG. Transcriptome-wide association analysis genes at previously associated POAG, analysis, conditional on disease status, implicated 97 statistically cell-specific loci. This work highlights power large-scale iPSC studies uncover context-specific profiles genetically complex