Taiwanese Study Using Population-based Polygenic Risk Score Effectively Predicted POAG

The most significant locus identified in the genome-wide association study was near the KYNU gene, which hasn’t been reported before in genetic POAG studies. KYNU encodes kynurenine, and the pathway this enzyme plays a key role in has been linked to mitochondrial dysfunction and a range of neurodegenerative conditions—including glaucoma—with reduced levels.  Photo: Michael Chaglasian, OD. Click image to enlarge. Glaucoma is a leading cause of blindness worldwide, and with heritability of primary open-angle glaucoma (POAG) being around 70%, identifying those at higher risk is crucial in providing timely and adequate care. Genetic screening is especially useful for POAG, as disease onset is often asymptomatic and clinical assessments and imaging in early detection is limited, thus researchers aim to identify subsets of vulnerable patients.In particular, a study appearing in American Journal of Ophthalmology looks at a Taiwanese population, since the East Asian region has been not as heavily studied in terms of creating polygenic risk scores (PRS) as those with European ancestry. The retrospective investigation included 3,064 POAG patients and 8,247 individuals without a glaucoma diagnosis who were over the age of 70. After analysis, it was found that the top 10% of the PRS had a 1.64-fold increased risk of developing POAG than those in the lowest quartile. Of those with POAG, a higher mean PRS was associated significantly with use of more than two classes of topical medications. The top 50% of the PRS also had an annual average decline of 1.79% in visual field index compared with the bottom 50%. Effectively, this PRS predicted POAG risk in Taiwanese people to be associated with increased disease severity and rapid progression.Upon discussion, the authors of the study elaborate that the association of more than two medication classes suggests that a PRS may serve as a marker of disease severity and treatment intensity. They cite that prior investigations have shown an increase in drug class number was predictive of subsequent treatment escalation, including further addition of medications classes or initiating laser or surgical interventions within 12 to 24 months. The participants in the current study who had higher PRS’ also had greater visual field index decline. As such, the authors argue that “these findings support the potential utility of PRS as a tool for risk stratification in clinical settings, particularly for identifying individuals who may benefit from closer monitoring and earlier intervention.”Although the authors do additionally note that POAG risk in those with a high PRS was only modest, that the model may still support early detection of those at high risk. The link of higher PRS with increased medication burden and visual field progression, they believe, suggests a potential role of genetic predisposition in disease severity and treatment response.Related to this, they convey “these findings may help inform personalized risk assessment, facilitate earlier referral and guide decisions regarding treatment intensity and follow-up strategies.”Click here for the journal source. Huang YC, Liao WL, Lin HJ, et al. Prediction of risk, severity, and progression of primary open-angle glaucoma in a Taiwanese population based on polygenic risk scores. Am J Ophthalmol. September 26, 2025. [Epub ahead of print]. This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.