Association of Polygenic Scores for Glaucoma With Measures of Retinal Ganglion Cell Integrity in Young and Older Adults

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. Design: Cross-sectional and cohort analyses Participants: Young (<30 years; n = 1400) and older (45+ years; n∼ 3,500) community-based adults. 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. Main outcome measures: Intraocular pressure (IOP), peripapillary retinal nerve fibre layer (pRNFL) thickness, and Bruch's membrane opening minimum rim width (BMO-MRW). 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. 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.