Evidence map›Paper›PMID 41130539›Full record

ArticleOphthalmology. Glaucoma

A Multitrait Polygenic Risk Score for Open-Angle Glaucoma Stratifies Risk of Pigmentary Glaucoma in Pigment Dispersion Syndrome.

Antonia Kolovos, Ayub Qassim, Henry N Marshall, Thi Thi Nguyen, Joshua Schmidt, Mark M Hassall, Victoria Tang, Giorgina Maxwell, John Landers, Richard Mills and 22 more

Abstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Ophthalmology. Glaucoma. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

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0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

32 authors.

Antonia KolovosFlinders Eye and Vision, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia; Department of Ophthalmology, Flinders Medical Centre, Adelaide, South Australia, Australia. Electronic address: antonia.kolovos@flinders.edu.au.
Ayub QassimFlinders Eye and Vision, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia; Department of Ophthalmology, Flinders Medical Centre, Adelaide, South Australia, Australia.
Henry N MarshallFlinders Eye and Vision, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia.
Thi Thi NguyenFlinders Eye and Vision, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia; Department of Ophthalmology, Flinders Medical Centre, Adelaide, South Australia, Australia.
Joshua SchmidtFlinders Eye and Vision, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia.
Mark M HassallFlinders Eye and Vision, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia; Department of Ophthalmology, Flinders Medical Centre, Adelaide, South Australia, Australia.
Victoria TangFlinders Eye and Vision, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia.
Giorgina MaxwellFlinders Eye and Vision, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia.
John LandersFlinders Eye and Vision, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia; Department of Ophthalmology, Flinders Medical Centre, Adelaide, South Australia, Australia.
Richard MillsFlinders Eye and Vision, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia; Department of Ophthalmology, Flinders Medical Centre, Adelaide, South Australia, Australia.
Stewart LakeFlinders Eye and Vision, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia; Department of Ophthalmology, Flinders Medical Centre, Adelaide, South Australia, Australia.
Stuart L GrahamFaculty of Medicine, Health and Human Sciences, Ophthalmology and Vision Science, Macquarie University, Sydney, New South Wales, Australia.
Angela SchulzFaculty of Medicine, Health and Human Sciences, Ophthalmology and Vision Science, Macquarie University, Sydney, New South Wales, Australia.
Anna GalanopoulosOphthalmic Research Laboratories, University of Adelaide, Adelaide Health and Medical Sciences Building, Adelaide, South Australia, Australia.
Robert J CassonOphthalmic Research Laboratories, University of Adelaide, Adelaide Health and Medical Sciences Building, Adelaide, South Australia, Australia.
Ivan GoldbergDiscipline of Ophthalmology, University of Sydney, Sydney Eye Hospital, Sydney, New South Wales, Australia.
Michael CooteCentre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia.
Stephen BestEye Department, Greenlane Clinical Centre, Auckland District Health Board, Auckland, New Zealand.
Jed LusthausDiscipline of Ophthalmology, University of Sydney, Sydney Eye Hospital, Sydney, New South Wales, Australia.
Paul R HealeyDepartment of Ophthalmology, Centre for Vision Research, Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia.
Leslie BurnettGenomics and Inherited Diseases, Garvan Institute of Medical Research, Sydney, New South Wales, Australia; Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia.
Marc Töteberg-HarmsDepartment of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, Iowa; Institute for Vision Research, University of Iowa, Iowa City, Iowa.
Erin A BoeseDepartment of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, Iowa; Institute for Vision Research, University of Iowa, Iowa City, Iowa.
Andrew E PouwDepartment of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, Iowa; Institute for Vision Research, University of Iowa, Iowa City, Iowa.
Puya GharahkhaniStatistical Genetics Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
Todd ScheetzDepartment of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, Iowa; Institute for Vision Research, University of Iowa, Iowa City, Iowa.
Alex W HewittCentre for Ophthalmology and Visual Science, University of Western Australia, Lions Eye Institute, Perth, Western Australia, Australia; Department of Ophthalmology, Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
Stuart MacGregorStatistical Genetics Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
Owen M SiggsGenomics and Inherited Diseases, Garvan Institute of Medical Research, Sydney, New South Wales, Australia; Faculty of Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia.
Emmanuelle SouzeauFlinders Eye and Vision, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia.
John H FingertDepartment of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, Iowa; Institute for Vision Research, University of Iowa, Iowa City, Iowa.
Jamie E CraigFlinders Eye and Vision, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia; Department of Ophthalmology, Flinders Medical Centre, Adelaide, South Australia, Australia.

Funding

Foundational Biology of Glaucoma GWAS LociR01EY035679 · NEI · UNIVERSITY OF IOWA · PI Michael G Anderson, JOHN H FINGERT · 2024 to 2026
$1.9M
Molecular Genetics of Norma Tension GlaucomaR01EY023512 · NEI · UNIVERSITY OF IOWA · PI FINGERT, JOHN H, MULLINS, ROBERT FOSTER · 2014 to 2017
$1.8M
Genetic Factors for Glaucoma in the OHTS; Risk, Progression and MechanismR01EY035266 · NEI · UNIVERSITY OF IOWA · PI JOHN H FINGERT, MAE O GORDON · 2023 to 2026
$1.6M
NEI NIH HHS R01 EY023512NEI NIH HHS R01 EY035266NEI NIH HHS R01 EY035679
6 · The paper itself

Abstract

objectivePigment dispersion syndrome (PDS) is a known risk factor for glaucoma, with at least 1 in 10 patients with PDS developing glaucoma. There are no standardized clinical tools to stratify the risk of glaucoma onset or progression in the context of PDS. This study investigated whether multitrait polygenic risk scores (PRSs) 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.

designCross-sectional study of 2 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).

participantsParticipants of European ancestry with PDS were classified as PDS-Glaucoma (n = 288), PDS-Glaucoma Suspect (n = 110), or PDS-No Glaucoma (n = 69).

methodsPreviously 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.

main outcome measuresOdds of pigmentary glaucoma and odds of clinically relevant outcomes.

resultsParticipants from ANZRAG with PDS in the top quintile of an open-angle glaucoma-PRS had greater odds of glaucoma diagnosis compared with the bottom quintile (adjusted odds ratio [OR], 5.29; 95% confidence interval [CI], 1.57-21.28; P = 0.011). This observation was replicated among participants with PDS from the University of Iowa (adjusted OR, 4.07; 95% CI, 1.24-13.85; P = 0.021). Among those with PDS-Glaucoma across both cohorts combined, participants in the top quintile of glaucoma-PRS compared with the bottom quintile were diagnosed 8 years earlier (95% CI, 5.17-10.41; P < 0.001), recorded a maximum IOP 8 mmHg 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.

conclusionsA multitrait PRS for open-angle glaucoma stratifies risk of glaucoma onset and disease severity among individuals with PDS. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Indexed as

Exfoliation SyndromeGlaucoma, Open-AngleIntraocular PressureMultifactorial InheritanceVisual FieldsAgedAustraliaCross-Sectional StudiesDisease ProgressionFemaleFollow-Up StudiesGenetic Risk ScoreHumansMaleMiddle AgedNew ZealandGeneticsGlaucomaPigmentary glaucomaPigment dispersion syndromePolygenic risk

Identifiers

PMID41130539
PMCPMC12797852

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.