Ophthalmology. Glaucoma · 2026
Primary Open Angle Glaucoma Polygenic Risk Score is Associated with Disease Progression.
СтатьяНазвание и аннотация: Перевод в очереди
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Bineshfar Niloufar, Aziz Kanza, Zhao Hetince, Zhao Yan, Singh Parmar Uday Pratap, Thi Vy Ha My, Rocheleau Ghislain, Do Ron, Kang Jae H, Segrè Ayellet V, Pasquale Louis R, Wiggs Janey L, Zebardast Nazlee
Аннотация
PURPOSE: To evaluate whether a polygenic risk score (PRS) for primary open-angle glaucoma (POAG) is associated with open-angle glaucoma (OAG) progression and treatment burden in a multiancestry population.
DESIGN: Longitudinal cohort study.
SUBJECTS: A total of 950 individuals with OAG and serial Humphrey visual field (VF) testing were included, comprising 713 participants from the Mass General Brigham Biobank and 237 from the Mount Sinai BioMe Biobank.
METHODS: A POAG PRS was generated using summary statistics from a cross-ancestry genome-wide association study. Association between PRS and VF progression, defined as a mean deviation slope worse than -0.25 dB/year, was tested with logistic regression models adjusted for age, sex, and ancestry. Associations with treatment burden, defined by a weighted score of medications, laser, and surgical interventions, were analyzed using logistic regression. Association between PRS and surgical interventions were assessed using Cox proportional hazards models.
MAIN OUTCOME MEASURES: OAG progression described by mean deviation slope and treatment intensity.
RESULTS: Among 950 individuals with OAG, the mean age at baseline was 71.2 ± 10.5 years; 54.7% were female, and 65.5% were of European descent. The median follow-up duration was 6.5 years. Each standard deviation (SD) increase in PRS was associated with a faster rate of VF decline (β = -0.02 dB/year per SD higher PRS; 95% confidence interval [CI], -0.04 to -0.01; P = 0.007) and 22% higher odds of progression (odds ratio = 1.22 per SD higher PRS; 95% CI, 1.04-1.42; P = 0.014). Higher PRS was also associated with greater treatment burden (odds ratio = 1.47 per SD; 95% CI, 1.27-1.71; P < 0.001). In the Mass General Brigham cohort, higher PRS predicted shorter time to glaucoma procedures (hazard ratio = 1.34 per SD; 95% CI, 1.12-1.59; P = 0.001), and this association persisted among eyes with normal or mild baseline disease severity (hazard ratio = 1.33 per SD; 95% CI, 1.10-1.60; P = 0.003).
CONCLUSIONS: In 2 independent biobank cohorts, higher POAG PRS was associated with faster VF progression and greater treatment burden in OAG. These findings support the potential utility of genetic risk profiling for prognostication of disease trajectory and management intensity in glaucoma.
FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
DESIGN: Longitudinal cohort study.
SUBJECTS: A total of 950 individuals with OAG and serial Humphrey visual field (VF) testing were included, comprising 713 participants from the Mass General Brigham Biobank and 237 from the Mount Sinai BioMe Biobank.
METHODS: A POAG PRS was generated using summary statistics from a cross-ancestry genome-wide association study. Association between PRS and VF progression, defined as a mean deviation slope worse than -0.25 dB/year, was tested with logistic regression models adjusted for age, sex, and ancestry. Associations with treatment burden, defined by a weighted score of medications, laser, and surgical interventions, were analyzed using logistic regression. Association between PRS and surgical interventions were assessed using Cox proportional hazards models.
MAIN OUTCOME MEASURES: OAG progression described by mean deviation slope and treatment intensity.
RESULTS: Among 950 individuals with OAG, the mean age at baseline was 71.2 ± 10.5 years; 54.7% were female, and 65.5% were of European descent. The median follow-up duration was 6.5 years. Each standard deviation (SD) increase in PRS was associated with a faster rate of VF decline (β = -0.02 dB/year per SD higher PRS; 95% confidence interval [CI], -0.04 to -0.01; P = 0.007) and 22% higher odds of progression (odds ratio = 1.22 per SD higher PRS; 95% CI, 1.04-1.42; P = 0.014). Higher PRS was also associated with greater treatment burden (odds ratio = 1.47 per SD; 95% CI, 1.27-1.71; P < 0.001). In the Mass General Brigham cohort, higher PRS predicted shorter time to glaucoma procedures (hazard ratio = 1.34 per SD; 95% CI, 1.12-1.59; P = 0.001), and this association persisted among eyes with normal or mild baseline disease severity (hazard ratio = 1.33 per SD; 95% CI, 1.10-1.60; P = 0.003).
CONCLUSIONS: In 2 independent biobank cohorts, higher POAG PRS was associated with faster VF progression and greater treatment burden in OAG. These findings support the potential utility of genetic risk profiling for prognostication of disease trajectory and management intensity in glaucoma.
FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.