Elevated polygenic risk score is associated with increased risk of glaucoma

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

In more than 1,000 patients, each higher PRS decile increased the risk of POAG by 1.36%, with a conversion rate of 9.52% for the lowest decile, said Nazry Zeberdast, MD, of Massachusetts Eye and Otolaryngology and Harvard Medical School. reported that it ranged from 21.81% to the highest decile. Friends and colleagues in Boston.

Comparing low-risk and high-risk PRS tertiles showed a 2-fold increased 20-year POAG risk in patients of European and African descent. JAMA Ophthalmology.

“These findings suggest that 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. are writing.

The predictive model was significantly improved by adding PRS as a covariate compared to the study's baseline model (P<0.001), Zebardast and team reported. Each one standard deviation above his PRS gave an average hazard ratio of 1.25 (95% CI 1.13-1.44) for developing POAG.

“POAG is a highly heritable disease, with 127 common risk mutations identified to date,” the researchers explained. “Each variant has a small effect individually, but together they can be used to measure the overall genetic burden due to PRS. Genotyping can be done cheaply once in a lifetime and It will be possible to calculate PRS for a disease.”

in Attached commentary“The key finding of this study is that PRS can independently predict the development of POAG in individuals with “That is true.” Ocular hypertension is revolutionary and timely. ”

Current risk analysis strategies often fail to detect diseases until they are advanced enough to cause irreversible damage, the researchers wrote. “His introduction of PRS as a predictive tool may result in a paradigm shift and the potential to identify at-risk individuals before the clinical onset of disease.”

“For example, patients with high PRS may benefit from more frequent monitoring, early intervention, and possibly a more aggressive treatment approach to prevent or delay the onset of POAG,” researchers wrote. added. “Conversely, people with low PRS may require less intensive monitoring, potentially reducing the burden of medical costs and unnecessary interventions.”

Main findings Findings from the Ocular Hypertension Treatment Study showed that topical intraocular hypertension medications are effective in delaying or preventing the onset of POAG in patients with elevated intraocular pressure.

A post-hoc analysis of this study obtained data from 22 sites in the United States with an average follow-up of 14 years. A total of 1,636 participants were followed from February 1994 to December 2008, 1,077 were enrolled in the auxiliary genetics study, and 1,009 met the criteria for this analysis.

Of the 1,009 participants, the average age was 55.9 years, 55.7% were female, 757 were of European descent, and 252 were of African descent. The average PRS was significantly higher for 350 POAG converters compared to 659 non-converters (0.24 vs. -0.12; P<0.001).

PRS was calculated using summary statistics from a meta-analysis of POAG genome-wide association studies across ancestry. PRS was trained using her 8,813,496 variants from participants across his 449,186 ancestors in the UK Biobank.

Zebardast and his team believe that the relatively small size of the study cohort, the low proportion of participants with confirmed POAG, and the lack of regular follow-up after 15 years were all limitations of the study. I admitted something.