Journal article
A multitrait polygenic risk score for open-angle glaucoma stratifies risk of pigmentary glaucoma in pigment dispersion syndrome
Ophthalmology. Glaucoma, Vol.9(2), pp.193-201
03/2026
DOI: 10.1016/j.ogla.2025.10.005
PMCID: PMC12797852
PMID: 41130539
Abstract
Pigment dispersion syndrome (PDS) is a known risk factor for glaucoma, with at least 1 in 10 PDS patients developing glaucoma. There are no standardized clinical tools to stratify risk of glaucoma onset or progression in the context of PDS. This study investigated whether multitrait polygenic risk scores (PRS) built from variants collectively associated with open-angle glaucoma, intraocular pressure (IOP), and vertical cup:disc ratio (VCDR) could stratify individuals with PDS for their risk of glaucoma development.
Cross-sectional study of two independent PDS cohorts: the Australian and New Zealand Registry of Advanced Glaucoma (ANZRAG, n=264), and the Glaucoma Services at the University of Iowa Carver College of Medicine (n=203).
Participants of European ancestry with PDS were classified as PDS-Glaucoma (n=288), PDS-Glaucoma Suspect (n=110), or PDS-No Glaucoma (n=69).
Previously published and validated PRS for open-angle glaucoma, IOP, and VCDR were expressed as a percentile or quintile of an ancestrally-matched normal population. Multivariable logistic and linear regressions, and survival analyses were performed.
Odds of pigmentary glaucoma, and odds of clinically-relevant outcomes.
Participants from ANZRAG with PDS in the top quintile of an open-angle Glaucoma-PRS had greater odds of glaucoma diagnosis compared to the bottom quintile (adjusted OR 5.29, 95% CI 1.57-21.28, p=0.011). This observation was replicated amongst participants with PDS from the University of Iowa (adjusted OR 4.07, 95% CI 1.24-13.85, p=0.021). Amongst those with PDS-Glaucoma across both cohorts combined, participants in the top quintile of Glaucoma-PRS compared to the bottom quintile were diagnosed 8 years earlier (95% CI 5.17-10.41, p<0.001), recorded a maximum IOP 8mmHg higher (95% CI 2.89-11.95, p=0.001), were at greater risk of escalation to incisional surgery (adjusted OR 1.37, 95% CI 1.03-1.87, p=0.038), and were at greater risk of additional incisional surgeries to the same eye (adjusted OR 1.27, 95% CI 1.08-1.52, p=0.006). A PRS for IOP also differentiated pigmentary glaucoma status; a PRS for VCDR did not.
A multitrait PRS for open-angle glaucoma stratifies risk of glaucoma onset and disease severity amongst individuals with PDS.
Details
- Title: Subtitle
- A multitrait polygenic risk score for open-angle glaucoma stratifies risk of pigmentary glaucoma in pigment dispersion syndrome
- Creators
- Antonia Kolovos - Flinders Medical CentreAyub Qassim - Flinders Medical CentreHenry Marshall - Flinders UniversityThi Thi Nguyen - Flinders Medical CentreJoshua Schmidt - Flinders UniversityMark M Hassall - Flinders Medical CentreVictoria Tang - Flinders UniversityGiorgina Maxwell - Flinders UniversityJohn Landers - Flinders Medical CentreRichard Mills - Flinders Medical CentreStewart Lake - Flinders Medical CentreStuart Graham - Macquarie UniversityAngela Schulz - Macquarie UniversityAnna Galanopoulos - The University of AdelaideRobert J Casson - The University of AdelaideIvan Goldberg - Sydney HospitalMichael Coote - Centre for Eye Research AustraliaStephen Best - Auckland District Health BoardJed Lusthaus - Sydney HospitalPaul R Healey - The University of SydneyLeslie Burnett - Garvan Institute of Medical ResearchMarc Töteberg-Harms - University of IowaErin A Boese - University of IowaAndrew E Pouw - University of IowaPuya Gharahkhani - QIMR Berghofer Medical Research InstituteTodd Scheetz - University of IowaAlex W Hewitt - University of TasmaniaStuart MacGregor - QIMR Berghofer Medical Research InstituteOwen M Siggs - Garvan Institute of Medical ResearchEmmanuelle Souzeau - Flinders UniversityJohn H Fingert - University of IowaJamie E Craig - Flinders Medical Centre
- Resource Type
- Journal article
- Publication Details
- Ophthalmology. Glaucoma, Vol.9(2), pp.193-201
- DOI
- 10.1016/j.ogla.2025.10.005
- PMID
- 41130539
- PMCID
- PMC12797852
- NLM abbreviation
- Ophthalmol Glaucoma
- ISSN
- 2589-4196
- eISSN
- 2589-4196
- Publisher
- Elsevier
- Grant note
- Australian National Health and Medical Research Council (NHMRC): 1150144 Australian NHMRCBrightFocus FoundationSnow Medical Research FoundationNIH: RO1EY035266, EY035679 Research to Prevent Blindness
J.E.C. and S.M. acknowledge Program (grant no.: 1150144) funding from the Australian National Health and Medical Research Council (NHMRC) . J.E.C., S.M., E.S., and P.G. acknowledge Fellowship and Investigator grant funding from the Australian NHMRC. P.G. acknowledges support from the BrightFocus Foundation. O.M.S. acknowledges support from the Snow Medical Research Foundation. J.H.F. and T.S. acknowledge support from the grant no.: NIH RO1EY035266 and grant no.: EY035679 and Research to Prevent Blindness. The sponsor or funding organization had no role in the design or conduct of this research.
- Language
- English
- Electronic publication date
- 10/21/2025
- Date published
- 03/2026
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Ophthalmology and Visual Sciences
- Record Identifier
- 9985019152002771
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