| Title: | Polygenic Risk Prediction for Normal-Tension Glaucoma |
| Journal: | Investigative Ophthalmology & Visual Science |
| Published: | 1 Jul 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40590803/ |
| DOI: | https://doi.org/10.1167/iovs.66.9.4 |
| URL: | https://iovs.arvojournals.org/arvo/content_public/journal/iovs/938720/i1552-5783-66-9-4_1751363117.77615.pdf |
Publication 16353
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Abstract
Purpose: Normal-tension glaucoma (NTG) is a subtype of glaucoma characterized by optic nerve damage in the setting of normal intraocular pressure. Polygenic risk scores (PRSs) have shown potential to assist with risk prediction in glaucoma, but to date no comprehensive studies have evaluated the predictive ability of PRSs for NTG.</p>
Methods: We utilized genome-wide association study (GWAS) summary data for NTG from a European cohort to estimate the variant weights and construct PRSs. The PRSs were computed using both the SBayesRC and clumping and thresholding (C+T) methods in 317 European ancestry NTG cases and 634 controls from the National Institutes of Health All of Us dataset. To validate our findings, we used the Genetics of Glaucoma (GOG) dataset for NTG cases (n = 89) and the QSkin Sun and Health Study (QSkin) dataset for controls (n = 267).</p>
Results: We applied the SBayesRC method, which incorporates genome functional annotation, to compare results across both studies. Logistic regression was performed to assess the association between PRSs and NTG. SBayesRC analysis demonstrated that the NTG PRS was significantly associated with NTG, yielding an odds ratio per standard deviation of 1.53 (95% confidence interval [CI], 1.32-1.77; P = 6.86 × 10⁻9) in the All of Us dataset and 1.83 (95% CI, 1.42-2.38; P = 4.01 × 10⁻6) in the combined GOG and QSkin dataset. The C+T method produced results similar to those for SBayesRC.</p>
Conclusions: Despite the limited sample size of current NTG GWASs, our findings suggest that NTG-specific PRSs hold promise for risk prediction. Future large-scale GWASs for NTG may enable the development of clinically relevant PRSs, improving early detection and personalized risk assessment for this challenging phenotype.</p>
12 Keywords
- Aged
- Female
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Humans
- Intraocular Pressure
- Low Tension Glaucoma
- Male
- Middle Aged
- Multifactorial Inheritance
- Polymorphism, Single Nucleotide
- Risk Factors
10 Authors
- Maryam Marzban
- Santiago Diaz Torres
- Regina Yu
- Weixiong He
- David A. Mackey
- Ayellet V. Segrè
- Janey Wiggs
- Stuart MacGregor
- Puya Gharahkhani
- on behalf of the International Glaucoma Genetics Consortium
1 Application
| Application ID | Title |
|---|---|
| 25331 | Gene mapping and genetic correlation across complex traits |
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