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SUMMARY:Large-scale GWAS integrated with fine-mapping and single-cell analyses prioritizes effector genes\, cell-contexts of glaucoma risk
DESCRIPTION:Statistical Bioinformatics SeminarSpeaker: Han Wang\, Peking University \n\n\n\nThis is an online event held via Zoom.Zoom link: https://uni-sydney.zoom.us/j/85114748391 \n\n\n\n\n\n\n\n\n\nPrimary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide\, and the genetic architecture of POAG at cellular level remains incompletely understood. In this study\, we conducted a large-scale genome-wide association study of POAG involving approximately 3 million individuals (97\,229 cases) and identified 495 loci (198 novel). External evaluation in 23andMe Research Institute (114\,468 cases and 3\,525\,660 controls) showed that 412 (84.6%) had P < 0.0001 after Bonferroni correction. Integrating multi-omics datasets with advanced fine-mapping approaches\, we developed a glaucoma gene prioritization framework and identified 285 effector genes. Single-cell RNA-seq analysis revealed retinal cell types including astrocytes\, Müller glia\, retinal pigment epithelial cells\, and retinal ganglion cells. Using our new scRNA-seq in primary trabecular meshwork cells (TMCs)\, we further prioritized TMC-context putative genes\, including ADAM15 and GAS7. Finally\, drug-repurposing analyses identified therapeutic target hypotheses for POAG. Together\, these findings provide a comprehensive genetic architecture for POAG\, highlighting novel effector genes and cellular contexts\, and offering potential drug repurposing opportunities. \n\n\n\n\n\n\nSubscribe to our seminar mailing list\n\n\n\n\n→\n\n\n\n\n\n\n\nFind out more about the Statistical Bioinformatics seminar series\n\n\n\n\n\n→\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nHan Wang\n\n\n\nHan Wang is a PhD student (work with Dr Xikun Han) in Epidemiology and Biostatistics at Peking University. His research lies at the intersection of statistical genetics and ophthalmology genetics\, focusing on dissecting the genetic architecture of glaucoma and retinal diseases. He integrates large-scale GWAS\, single-cell RNA/ATAC sequencing\, and gene prioritization to identify effector genes and to repurpose existing drugs for glaucoma.
URL:https://spds.sydney.edu.au/event/predicting-cellular-perturbations-biological-benchmarks-and-ai-assisted-model-discovery/
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