Luben, Robert N;
Biradar, Mahantesh I;
Stuart, Kelsey V;
Hu, Ruiqi;
Sun, Zihan;
Li, Zheng;
Wang, Ningli;
... Khawaja, Anthony P; + view all
(2025)
GWAS for primary angle-closure glaucoma identifies loci related to ocular biometry and morphology.
Nature Communications
, 16
, Article 10003. 10.1038/s41467-025-64949-z.
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Abstract
GWAS of primary angle-closure glaucoma have identified eight loci conferring risk in Asian populations. However, it remains unclear whether the genetic risk factors for the disease are consistent across different populations. Here, we present a discovery GWAS for primary angle-closure glaucoma in Europeans using the UK Biobank. We replicate our findings in six independent European populations and compare these results with results from 14 Asian cohorts. Five genomic regions in the discovery cohort are associated at genome-wide significance, including two loci previously identified in Asian cohorts. We next meta-analyse the discovery and replication cohorts to identify six additional novel loci, all previously associated with refractive error. Mendelian randomisation provides evidence for a causal role of shorter axial length and hypermetropic refractive error on primary angle-closure glaucoma. A polygenic risk score derived from the European ancestry meta-analysis demonstrates significant associations with quantitative ocular traits - including a shallower anterior chamber and higher intraocular pressure - in the independent EPIC-Norfolk cohort. Finally, a multi-ancestry meta-analysis of all 21 European and Asian cohorts identifies 12 further novel loci. This work shows that genetic factors associated with a darker iris and hypermetropia confer risk for primary angle-closure glaucoma.
| Type: | Article |
|---|---|
| Title: | GWAS for primary angle-closure glaucoma identifies loci related to ocular biometry and morphology |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41467-025-64949-z |
| Publisher version: | https://doi.org/10.1038/s41467-025-64949-z |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Glaucoma, Angle-Closure, Humans, Genome-Wide Association Study, Genetic Predisposition to Disease, White People, Male, Asian People, Female, Polymorphism, Single Nucleotide, Aged, Middle Aged, Intraocular Pressure, Biometry, Risk Factors, United Kingdom, Multifactorial Inheritance, Genetic Loci, Mendelian Randomization Analysis, White |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Population, Policy and Practice Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10217340 |
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