| Title: | Association of Polygenic Scores for Glaucoma With Measures of Retinal Ganglion Cell Integrity in Young and Older Adults |
| Journal: | American Journal of Ophthalmology |
| Published: | 26 Sep 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41016518/ |
| DOI: | https://doi.org/10.1016/j.ajo.2025.09.042 |
Publication 19403
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Abstract
PURPOSE: Polygenic scores (PGS) for glaucoma is predictive of the disease in older adults. This study tested the hypothesis that multitrait PGS for primary open-angle glaucoma (POAG) and its associated traits are associated with glaucoma endophenotypes from a young age, but with larger effects in older adults.</p>
DESIGN: Cross-sectional and cohort analyses PARTICIPANTS: Young (<30 years; n = 1400) and older (45+ years; n∼ 3,500) community-based adults.</p>
METHODS: Participants underwent ocular tonometry, optical coherence tomography imaging, and genotyping. Their PGS for POAG, IOP, and vertical cup-to-disc ratio (VCDR) were generated. A subset of young participants (n∼614) had follow-up measurements 8 years later. Cross-sectional associations in both cohorts and the 8-year change in the young cohort were analysed against each PGS.</p>
MAIN OUTCOME MEASURES: Intraocular pressure (IOP), peripapillary retinal nerve fibre layer (pRNFL) thickness, and Bruch's membrane opening minimum rim width (BMO-MRW).</p>
RESULTS: IOP-PGS explained 4 and 8% of the variance in IOP in the young and older cohorts. Weak associations between pRNFL thickness and all 3 PGS were observed in the older group, but none were significant in the young participants. All 3 PGS were significantly associated with BMO-MRW, explaining 0.3-14.5% and 0.1-12.8% of the phenotypic variance in the older and younger cohorts, respectively. None of the PGS were associated with longitudinal IOP or pRNFL change in the young cohort.</p>
CONCLUSIONS: Associations between PGS and optic disc measures were present from young adulthood, but the effect sizes were greater in older adults. This, coupled with the lack of associations in the 8-year change in the young adults, suggests that glaucoma-related genetic effects on the optic nerve are not apparent until older age.</p>
20 Keywords
- Adult
- Aged
- Aged, 80 and over
- Cross-Sectional Studies
- Female
- Follow-Up Studies
- Genotype
- Glaucoma, Open-Angle
- Humans
- Intraocular Pressure
- Male
- Middle Aged
- Multifactorial Inheritance
- Nerve Fibers
- Optic Disk
- Retinal Ganglion Cells
- Tomography, Optical Coherence
- Tonometry, Ocular
- Visual Fields
- Young Adult
10 Authors
- Samantha Sze-Yee Lee
- Santiago Diaz Torres
- Gareth Lingham
- Seyhan Yazar
- Michael Hunter
- Jamie E Craig
- Alex W Hewitt
- Stuart Macgregor
- Puya Gharahkhani
- David A Mackey
1 Application
| Application ID | Title |
|---|---|
| 25331 | Gene mapping and genetic correlation across complex traits |
Enabling scientific discoveries that improve human health