Genetic risk for glaucoma increases with age

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An international collaborative research effort found that with aging, a higher genetic risk score is a stronger predictor of elevated intraocular pressure (IOP) and an increased chance of developing glaucoma.¹ The researchers, led by first author Jihye Kim, PhD, from the Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, published their findings in Investigative Ophthalmology and Visual Science.

In their report, the authors explained, “The main reason why people go blind from glaucoma is because the disease has an insidious onset, and patients present too late.^2,3 Genetic makeup is largely determined at birth. Thus, a properly timed recall-by-glaucoma polygenic risk score (PRS) approach might represent a viable screening strategy to facilitate early disease detection. The timing of such a prevention strategy must account for the age-related component of the disease and its fairly low incidence.”

The investigators cited studies that underscored their thesis. The studies found that the 5-year incidence of at least possible primary open-angle glaucoma (POAG) increased from 0.5% in participants aged 40 to 49 years to 4.1% in participants aged 60 to 69 years among White participants living in Melbourne, Australia,⁴ and the 4-year incidence of OAG increased from 1.2% in participants aged 40 to 49 years to 4.2% in participants aged 70 years or older among Black people living in Barbados.⁵

Determining the PRS

In the study under discussion, Kim and colleagues set out to determine the age groups for which a PRS would most effectively predict glaucomatous risk and help inform cost-effective methods for disease detection. They investigated if the relation between a multitrait glaucoma PRS (mtGPRS) and glaucoma, as well as glaucoma-related traits, was modified by age and sex among UK Biobank participants.

The researchers investigated the single-nucleotide polymorphisms of the participants that can reveal individuals’ risks for particular diseases. They calculated a genetic risk score for glaucoma (multitrait glaucoma PRS) for each person based on their DNA and divided the participants based on age: under 51, 51-57, 58-62, and 63 years and older. Finally, they studied the relationship between each genetic risk score and the participants’ IOP, the retinal structure, and whether they had glaucoma.

Researchers analyzed IOP data from 118,153 participants. For glaucoma prevalence, the researchers looked at a larger group of 192,283 participants, of whom 8982 had glaucoma.

Kim and colleagues reported, “Age significantly modified the relationship between the multitrait GPRS and IOP (P_interaction = 2.7e-27). The mean IOP differences (in mmHg)/standard deviation (SD) of multitrait GPRS were 0.95, 1.02, 1.18, and 1.24, respectively, across the four age quartiles.”

They also observed similar trends for glaucoma risk (odds ratio/SD of mtGPRS = 2.38, 2.57, 2.80, and 2.75, respectively; P_interaction = 1.0e-06).

The relationships between the multitrait GPRS and the inner retinal thickness (myelinated retinal nerve fiber layer and macular ganglion cell-inner plexiform layer) across the age groups were inconsistently modified by age (P_interaction ≥ 0.01).

The authors determined that with the increasing age of the participants, “a multitrait GPRS was a better predictor of higher IOP and glaucoma prevalence. It is useful to consider chronologic age with genetic information in designing glaucoma screening strategies.”

They advised that as genetic risk scoring for glaucoma becomes more readily available, those with the highest genetic predisposition should be prioritized for glaucoma screening. In the UK Biobank, those in the 58- to 62-year-old age group had the highest odds of having glaucoma., information that is useful for planning screening strategies for those currently undiagnosed individuals in the most vulnerable populations. Finally, resilience biomarkers related to younger age hold promise for mitigating the genetic predisposition to higher IOP and glaucoma in older individuals.

References:

1. Kim J, Kang JH, Wiggs JL, et al. Does age modify the relation between genetic predisposition to glaucoma and various glaucoma traits in the UK Biobank? Invest Ophthalmol Vis Sci. 2025;66: 57. doi: https://doi.org/10.1167/iovs.66.2.57

2. Grant WM, Burke JF, Jr. Why do some people go blind from glaucoma? Ophthalmology. 1982; 89: 991–998.

3. Susanna R, Jr, De Moraes CG, Cioffi GA, Ritch R. Why do people (still) go blind from glaucoma? Transl Vis Sci Technol. 2015;4:1.

4. Mukesh BN, McCarty CA, Rait JL, Taylor HR. Five-year incidence of open-angle glaucoma: the visual impairment project. Ophthalmology. 2002;109:1047–1051.

5. Leske MC, Connell AM, Wu SY, et al. Incidence of open-angle glaucoma: the Barbados Eye Studies. The Barbados Eye Studies Group. Arch Ophthalmol. 2001;119: 89–95.