A multi-trait open-angle glaucoma polygenic risk score stratifies risk of glaucoma diagnosis and severity in eyes with pseudoexfoliation.

IF 13.1 1区医学 Q1 OPHTHALMOLOGY

Ophthalmology Pub Date : 2025-02-24 DOI:10.1016/j.ophtha.2025.02.013

Antonia Kolovos, Ayub Qassim, Mark M Hassall, Henry Marshall, Joshua Schmidt, Thi Thi Nguyen, Weixiong He, Sean Mullany, Georgina Hollitt, Ella Berry, Victoria Tang, Tiger Zhou, Stewart Lake, Richard Mills, John Landers, Robert J Casson, Anna Galanopoulos, Stuart L Graham, Angela Schulz, Paul R Healey, Paul Mitchell, Ivan Goldberg, John Grigg, Jonathan Ruddle, David A Mackey, Kathryn P Burdon, Alex W Hewitt, Mathias Seviiri, Puya Gharahkhani, Emmanuelle Souzeau, Owen M Siggs, Stuart MacGregor, Jamie E Craig

{"title":"A multi-trait open-angle glaucoma polygenic risk score stratifies risk of glaucoma diagnosis and severity in eyes with pseudoexfoliation.","authors":"Antonia Kolovos, Ayub Qassim, Mark M Hassall, Henry Marshall, Joshua Schmidt, Thi Thi Nguyen, Weixiong He, Sean Mullany, Georgina Hollitt, Ella Berry, Victoria Tang, Tiger Zhou, Stewart Lake, Richard Mills, John Landers, Robert J Casson, Anna Galanopoulos, Stuart L Graham, Angela Schulz, Paul R Healey, Paul Mitchell, Ivan Goldberg, John Grigg, Jonathan Ruddle, David A Mackey, Kathryn P Burdon, Alex W Hewitt, Mathias Seviiri, Puya Gharahkhani, Emmanuelle Souzeau, Owen M Siggs, Stuart MacGregor, Jamie E Craig","doi":"10.1016/j.ophtha.2025.02.013","DOIUrl":null,"url":null,"abstract":"Objective: Pseudoexfoliation syndrome (PEX) is a known risk factor for glaucoma, but its individual clinical course ranges from no glaucoma to total blindness. This study investigated whether polygenic risk scores (PRS) built from variants collectively associated with open-angle glaucoma, intraocular pressure (IOP) and vertical cup:disc ratio (VCDR) can stratify individuals with pseudoexfoliation for their risk of glaucoma development.Design: Retrospective multicohort study of two glaucoma registries and one population-based cohort.Participants: For the primary analysis, participants (n=828) were classified as PEX-Glaucoma, PEX-Glaucoma Suspect, and PEX-No Glaucoma. For the secondary analysis, a cohort of participants (n=2459) were classified as PEX-Glaucoma, PEX-No Glaucoma, and Unaffected, and an independent cohort of participants (n=3360) were classified as primary open-angle glaucoma (POAG) and POAG-Suspect.Methods: Previously published and validated PRS for open-angle glaucoma, IOP and VCDR were expressed as a percentile, decile or tertile of an ancestrally-matched normal population. Multivariable logistic and linear regressions, and survival analyses were performed.Main outcome measures: Odds of pseudoexfoliative glaucoma, and odds of clinically-relevant outcomes.Results: Participants in the top tertile of the Glaucoma-PRS had greater odds of pseudoexfoliative glaucoma diagnosis (adjusted OR 4.22, 95% CI 2.62 - 6.88, p<0.001), greater odds of bilateral central vision loss (adjusted OR 3.43, 95% CI 1.49 - 8.99, p=0.007), and greater odds of bilateral incisional surgery (adjusted OR 3.35, 95% CI 1.33 - 10.24, p=0.018). Age of pseudoexfoliative glaucoma diagnosis was 1 year younger with each increasing Glaucoma-PRS decile (1.06 years, 95% CI 0.59-1.53, p<0.001). Manifest glaucoma participants with pseudoexfoliation had a comparatively lower Glaucoma-PRS than primary open-angle glaucoma counterparts.Conclusion: PRS for open-angle glaucoma, IOP and VCDR stratify risk of glaucoma development and disease severity amongst individuals with pseudoexfoliation syndrome.","PeriodicalId":19533,"journal":{"name":"Ophthalmology","volume":" ","pages":""},"PeriodicalIF":13.1000,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Ophthalmology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ophtha.2025.02.013","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Objective: Pseudoexfoliation syndrome (PEX) is a known risk factor for glaucoma, but its individual clinical course ranges from no glaucoma to total blindness. This study investigated whether polygenic risk scores (PRS) built from variants collectively associated with open-angle glaucoma, intraocular pressure (IOP) and vertical cup:disc ratio (VCDR) can stratify individuals with pseudoexfoliation for their risk of glaucoma development.

Design: Retrospective multicohort study of two glaucoma registries and one population-based cohort.

Participants: For the primary analysis, participants (n=828) were classified as PEX-Glaucoma, PEX-Glaucoma Suspect, and PEX-No Glaucoma. For the secondary analysis, a cohort of participants (n=2459) were classified as PEX-Glaucoma, PEX-No Glaucoma, and Unaffected, and an independent cohort of participants (n=3360) were classified as primary open-angle glaucoma (POAG) and POAG-Suspect.

Methods: Previously published and validated PRS for open-angle glaucoma, IOP and VCDR were expressed as a percentile, decile or tertile of an ancestrally-matched normal population. Multivariable logistic and linear regressions, and survival analyses were performed.

Main outcome measures: Odds of pseudoexfoliative glaucoma, and odds of clinically-relevant outcomes.

Results: Participants in the top tertile of the Glaucoma-PRS had greater odds of pseudoexfoliative glaucoma diagnosis (adjusted OR 4.22, 95% CI 2.62 - 6.88, p<0.001), greater odds of bilateral central vision loss (adjusted OR 3.43, 95% CI 1.49 - 8.99, p=0.007), and greater odds of bilateral incisional surgery (adjusted OR 3.35, 95% CI 1.33 - 10.24, p=0.018). Age of pseudoexfoliative glaucoma diagnosis was 1 year younger with each increasing Glaucoma-PRS decile (1.06 years, 95% CI 0.59-1.53, p<0.001). Manifest glaucoma participants with pseudoexfoliation had a comparatively lower Glaucoma-PRS than primary open-angle glaucoma counterparts.

Conclusion: PRS for open-angle glaucoma, IOP and VCDR stratify risk of glaucoma development and disease severity amongst individuals with pseudoexfoliation syndrome.

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Ophthalmology 医学-眼科学

CiteScore

22.30

自引率

3.60%

发文量

412

审稿时长

18 days

期刊介绍： The journal Ophthalmology, from the American Academy of Ophthalmology, contributes to society by publishing research in clinical and basic science related to vision.It upholds excellence through unbiased peer-review, fostering innovation, promoting discovery, and encouraging lifelong learning.