GWAS for primary angle-closure glaucoma identifies loci related to ocular biometry and morphology
Issued Date
2025-12-01
Resource Type
eISSN
20411723
Scopus ID
2-s2.0-105021841100
Journal Title
Nature Communications
Volume
16
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Nature Communications Vol.16 No.1 (2025)
Suggested Citation
Luben R.N., Biradar M.I., Stuart K.V., Hu R., Sun Z., Li Z., Wang N., Do T., Pang C.P., Nakano M., Tashiro K., Ikeda Y., Tokuda Y., Tanaka M., Omi N., Ueno M., Sotozono C., Kinoshita S., Mori K., Kitnarong N., Fea A., Melo M.B., Vasconcellos J.P.C., Costa V.P., Nongpiur M.E., Ho C.L., Perera S.A., Craig J.E., Kolovos A., Liza-Sharmini A.T., Leuenberger E.U., Park K.H., Vijaya L., George R., Aung T., Khor C.C., Foster P.J., Hysi P., Khawaja A.P. GWAS for primary angle-closure glaucoma identifies loci related to ocular biometry and morphology. Nature Communications Vol.16 No.1 (2025). doi:10.1038/s41467-025-64949-z Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/113164
Title
GWAS for primary angle-closure glaucoma identifies loci related to ocular biometry and morphology
Author(s)
Luben R.N.
Biradar M.I.
Stuart K.V.
Hu R.
Sun Z.
Li Z.
Wang N.
Do T.
Pang C.P.
Nakano M.
Tashiro K.
Ikeda Y.
Tokuda Y.
Tanaka M.
Omi N.
Ueno M.
Sotozono C.
Kinoshita S.
Mori K.
Kitnarong N.
Fea A.
Melo M.B.
Vasconcellos J.P.C.
Costa V.P.
Nongpiur M.E.
Ho C.L.
Perera S.A.
Craig J.E.
Kolovos A.
Liza-Sharmini A.T.
Leuenberger E.U.
Park K.H.
Vijaya L.
George R.
Aung T.
Khor C.C.
Foster P.J.
Hysi P.
Khawaja A.P.
Biradar M.I.
Stuart K.V.
Hu R.
Sun Z.
Li Z.
Wang N.
Do T.
Pang C.P.
Nakano M.
Tashiro K.
Ikeda Y.
Tokuda Y.
Tanaka M.
Omi N.
Ueno M.
Sotozono C.
Kinoshita S.
Mori K.
Kitnarong N.
Fea A.
Melo M.B.
Vasconcellos J.P.C.
Costa V.P.
Nongpiur M.E.
Ho C.L.
Perera S.A.
Craig J.E.
Kolovos A.
Liza-Sharmini A.T.
Leuenberger E.U.
Park K.H.
Vijaya L.
George R.
Aung T.
Khor C.C.
Foster P.J.
Hysi P.
Khawaja A.P.
Author's Affiliation
King's College London
Chinese University of Hong Kong
Università degli Studi di Torino
Universidade Estadual de Campinas
Seoul National University Hospital
UCL Great Ormond Street Institute of Child Health
Kyoto Prefectural University of Medicine
Duke-NUS Medical School
Siriraj Hospital
Moorfields Eye Hospital NHS Foundation Trust
Beijing Tongren Hospital, Capital Medical University
Universiti Sains Malaysia, Health Campus
Singapore Eye Research Institute
MRC Epidemiology Unit
A-Star, Genome Institute of Singapore
Medical Research Foundation, Chennai
Flinders Health and Medical Research Institute
VNU-University of Medicine and Pharmacy
University of the East, Philippines
Vietnam National Eye Hospital
Sørlandet Sykehus Arendal
Chinese University of Hong Kong
Università degli Studi di Torino
Universidade Estadual de Campinas
Seoul National University Hospital
UCL Great Ormond Street Institute of Child Health
Kyoto Prefectural University of Medicine
Duke-NUS Medical School
Siriraj Hospital
Moorfields Eye Hospital NHS Foundation Trust
Beijing Tongren Hospital, Capital Medical University
Universiti Sains Malaysia, Health Campus
Singapore Eye Research Institute
MRC Epidemiology Unit
A-Star, Genome Institute of Singapore
Medical Research Foundation, Chennai
Flinders Health and Medical Research Institute
VNU-University of Medicine and Pharmacy
University of the East, Philippines
Vietnam National Eye Hospital
Sørlandet Sykehus Arendal
Corresponding Author(s)
Other Contributor(s)
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.