{"doi":"10.1101/2022.05.14.22275022","title":"Integrating genetic regulation and single-cell expression with GWAS prioritizes causal genes and cell types for glaucoma","abstract":"Abstract Primary open-angle glaucoma (POAG), characterized by retinal ganglion cell death, is a leading cause of irreversible blindness worldwide; however, the 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 GWAS loci and of overlapping eQTLs and sQTLs in 49 GTEx tissues and retina prioritized causal genes for 60% of loci. These genes were enriched in pathways implicated in extracellular matrix organization, cell adhesion, and vascular development. Analysis of single-nucleus RNA-seq of glaucoma-relevant eye tissues revealed that the colocalizing genes and genome-wide POAG and IOP associations were enriched in specific cell types in the aqueous outflow pathways, retina, optic nerve head, peripapillary sclera, and choroid. This study nominated IOP-dependent and independent regulatory mechanisms, genes, and cell types that may contribute to POAG pathogenesis.","journal":"medRxiv","year":2022,"id":296370,"datarank":0.611630616585858,"base_score":4.07753744390572,"endowment":4.07753744390572,"self_citation_contribution":0.611630616585858,"citation_network_contribution":0.0,"self_endowment_contribution":0.611630616585858,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":58,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9445,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":33173,"name":"Wenjun Yan","orcid":"0000-0003-3568-4265","position":1,"is_corresponding":false},{"id":103618,"name":"John M. 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