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Higher polygenic risk score (PRS) was associated with an increased risk for primary open-angle glaucoma (POAG) in patients with ocular hypertension, according to a post-hoc analysis of the Ocular Hypertension Treatment Study.

Among over 1,000 patients, risk of POAG increased 1.36% with each higher PRS decile, with conversion ranging from 9.52% in the lowest decile to 21.81% in the highest decile, reported Nazlee Zebardast, MD, of Massachusetts Eye and Ear and Harvard Medical School in Boston, and colleagues.

Comparing the low-risk and high-risk PRS tertiles showed a twofold increase in 20-year POAG risk for patients of European and African ancestries, they detailed in .

"These findings suggest background genetic risk for POAG may help stratify patients with ocular hypertension and help clinicians and patients make decisions about early treatment," the authors wrote.

Prediction models significantly improved with the addition of PRS as a covariate compared with the study's baseline model (P<0.001), Zebardast and team reported. Each 1-standard-deviation-higher PRS conferred a mean hazard ratio of 1.25 (95% CI 1.13-1.44) for POAG onset.

"POAG is a highly heritable disease, with 127 identified common risk variants to date," they explained. "While each variant individually has a small effect, they can be used in the aggregate to measure overall genetic burden with a PRS. Genotyping can be done inexpensively once per lifetime and enable the calculation of a PRS for a wide range of diseases."

In an , Fei Li, MD, PhD, and Xiulan Zhang, MD, PhD, of Guangdong Provincial Clinical Research Center for Ocular Diseases in China, noted that "the study's key finding -- that a PRS can independently predict the onset of POAG in individuals with ocular hypertension -- is both groundbreaking and timely."

Current risk analysis strategies often fail to pick up disease until it's advanced to cause irreversible damage, they wrote. "The introduction of PRS as a predictive tool may lead to a paradigm shift, offering the possibility of identifying at-risk individuals before the clinical onset of the disease."

"For instance, patients with a high PRS may benefit from more frequent monitoring, earlier intervention, and possibly more aggressive treatment approaches to prevent or delay the onset of POAG," they added. "Conversely, those with a lower PRS may require less intensive surveillance, potentially reducing healthcare costs and the burden of unnecessary interventions."

from the Ocular Hypertension Treatment Study showed that topical ocular hypotensive medication was effective in delaying or preventing the onset of POAG in patients with elevated intraocular pressure.

For this post-hoc analysis of the study, data were taken from 22 U.S. sites with a mean follow-up of 14 years. A total of 1,636 participants were followed from February 1994 to December 2008 -- 1,077 were enrolled in an ancillary genetics study, and 1,009 met criteria for this analysis.

Of the 1,009 participants, mean age was 55.9, 55.7% were women, 757 were of European ancestry, and 252 were of African ancestry. Mean PRS was significantly higher for the 350 POAG converters compared with the 659 non-converters (0.24 vs -0.12, P<0.001).

PRS was calculated using summary statistics from a cross-ancestry POAG genome-wide association study meta-analysis. The PRS was trained using 8,813,496 variants from 449,186 cross-ancestry participants in the U.K. Biobank.

Zebardast and team acknowledged that the relatively small size of the study cohort, the low proportion of participants with confirmed POAG, and loss to regular follow-up after 15 years were all limitations to the study.

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