Polygenic Risk Prediction for Normal-Tension Glaucoma

Area of Science:

• Ophthalmology
• Genetics
• Statistical Genomics

Background:

• Normal-tension glaucoma (NTG) is characterized by optic nerve damage with normal intraocular pressure.
• Polygenic risk scores (PRSs) are emerging tools for glaucoma risk prediction.
• No comprehensive studies have evaluated PRS predictive ability specifically for NTG.

Purpose of the Study:

• To evaluate the predictive ability of PRSs for normal-tension glaucoma (NTG).
• To construct and validate NTG-specific PRSs using genome-wide association study (GWAS) data.

Main Methods:

• Utilized GWAS summary data from a European cohort to develop PRSs for NTG.
• Employed SBayesRC and clumping and thresholding (C+T) methods for PRS computation.
• Validated PRSs in independent European ancestry datasets (All of Us, GOG, QSkin).

Main Results:

• NTG-specific PRSs, particularly using the SBayesRC method, showed significant association with NTG in both discovery and validation cohorts.
• Odds ratios per standard deviation indicated a notable increase in NTG risk associated with higher PRS values.
• The SBayesRC method, incorporating functional annotation, yielded robust predictive results.

Conclusions:

• NTG-specific PRSs demonstrate potential for glaucoma risk prediction, despite current limitations in NTG GWAS sample sizes.
• Future large-scale NTG GWASs could lead to clinically applicable PRSs for personalized risk assessment.
• Improved early detection and risk stratification for NTG may be achievable with advanced PRS development.