{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T11:48:26Z","timestamp":1788349706787,"version":"build-2803163510"},"reference-count":120,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T00:00:00Z","timestamp":1655078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2019s Horizon 2020 research","award":["661883"],"award-info":[{"award-number":["661883"]}]},{"name":"European Union\u2019s Horizon 2020 research","award":["B20150036"],"award-info":[{"award-number":["B20150036"]}]},{"name":"Rotterdamse Stichting Blindenbelangen","award":["661883"],"award-info":[{"award-number":["661883"]}]},{"name":"Rotterdamse Stichting Blindenbelangen","award":["B20150036"],"award-info":[{"award-number":["B20150036"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Primary open-angle glaucoma (POAG) is the most prevalent glaucoma subtype, but its exact etiology is still unknown. In this study, we aimed to prioritize the most likely \u2018causal\u2019 genes and identify functional characteristics and underlying biological pathways of POAG candidate genes. Methods: We used the results of a large POAG genome-wide association analysis study from GERA and UK Biobank cohorts. First, we performed systematic gene-prioritization analyses based on: (i) nearest genes; (ii) nonsynonymous single-nucleotide polymorphisms; (iii) co-regulation analysis; (iv) transcriptome-wide association studies; and (v) epigenomic data. Next, we performed functional enrichment analyses to find overrepresented functional pathways and tissues. Results: We identified 142 prioritized genes, of which 64 were novel for POAG. BICC1, AFAP1, and ABCA1 were the most highly prioritized genes based on four or more lines of evidence. The most significant pathways were related to extracellular matrix turnover, transforming growth factor-\u03b2, blood vessel development, and retinoic acid receptor signaling. Ocular tissues such as sclera and trabecular meshwork showed enrichment in prioritized gene expression (&gt;1.5 fold). We found pleiotropy of POAG with intraocular pressure and optic-disc parameters, as well as genetic correlation with hypertension and diabetes-related eye disease. Conclusions: Our findings contribute to a better understanding of the molecular mechanisms underlying glaucoma pathogenesis and have prioritized many novel candidate genes for functional follow-up studies.<\/jats:p>","DOI":"10.3390\/genes13061055","type":"journal-article","created":{"date-parts":[[2022,6,13]],"date-time":"2022-06-13T22:00:38Z","timestamp":1655157638000},"page":"1055","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Bioinformatic Prioritization and Functional Annotation of GWAS-Based Candidate Genes for Primary Open-Angle Glaucoma"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5680-5527","authenticated-orcid":false,"given":"Nigus G.","family":"Asefa","sequence":"first","affiliation":[{"name":"Department of Epidemiology, Unit of Genetic Epidemiology and Bioinformatics, University of Groningen, UMCG, Hanzeplein 1, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6492-5887","authenticated-orcid":false,"given":"Zoha","family":"Kamali","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Unit of Genetic Epidemiology and Bioinformatics, University of Groningen, UMCG, Hanzeplein 1, 9713 GZ Groningen, The Netherlands"},{"name":"Department of Bioinformatics, Isfahan University of Medical Sciences, Isfahan P.O. Box 81746-7346, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1089-0433","authenticated-orcid":false,"given":"Satyajit","family":"Pereira","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal 576104, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9048-3795","authenticated-orcid":false,"given":"Ahmad","family":"Vaez","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Unit of Genetic Epidemiology and Bioinformatics, University of Groningen, UMCG, Hanzeplein 1, 9713 GZ Groningen, The Netherlands"},{"name":"Department of Bioinformatics, Isfahan University of Medical Sciences, Isfahan P.O. Box 81746-7346, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nomdo","family":"Jansonius","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Groningen, UMCG, Hanzeplein 1, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur A.","family":"Bergen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Amsterdam University Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1949-2298","authenticated-orcid":false,"given":"Harold","family":"Snieder","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Unit of Genetic Epidemiology and Bioinformatics, University of Groningen, UMCG, Hanzeplein 1, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"R21","DOI":"10.1093\/hmg\/ddx184","article-title":"Genetics of glaucoma","volume":"26","author":"Wiggs","year":"2017","journal-title":"Hum. 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