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

Area of Science:

• Ophthalmology
• Genetics
• Glaucoma Research

Background:

• Pigment dispersion syndrome (PDS) is a significant risk factor for glaucoma, affecting at least 10% of patients.
• Current clinical tools lack standardization for assessing glaucoma risk in PDS patients.
• No established methods exist to stratify PDS individuals for glaucoma onset or progression risk.

Purpose of the Study:

• To evaluate the efficacy of multitrait polygenic risk scores (PRSs) in stratifying glaucoma risk among individuals with PDS.
• To investigate PRSs derived from variants associated with open-angle glaucoma, intraocular pressure (IOP), and vertical cup:disc ratio (VCDR).

Main Methods:

• A cross-sectional study involving two independent PDS cohorts: ANZRAG (n=264) and University of Iowa (n=203).
• Participants of European ancestry with PDS were categorized into PDS-Glaucoma, PDS-Glaucoma Suspect, and PDS-No Glaucoma groups.
• Validated PRSs for open-angle glaucoma, IOP, and VCDR were used, analyzed via logistic/linear regressions and survival analyses.

Main Results:

• Individuals in the top quintile of open-angle glaucoma PRS showed significantly higher odds of glaucoma diagnosis in both cohorts.
• Among PDS-Glaucoma patients, the top PRS quintile correlated with earlier diagnosis, higher maximum IOP, and increased risk of incisional surgery.
• A PRS for IOP also differentiated pigmentary glaucoma status, while a VCDR PRS did not.

Conclusions:

• Multitrait PRSs for open-angle glaucoma effectively stratify glaucoma onset risk in PDS patients.
• These PRSs also help determine disease severity and progression risk in individuals with PDS.
• This study highlights the potential of PRS in personalized risk assessment for PDS-related glaucoma.