Intrinsic Capacity, Polygenic Risk Score, and Risk of Glaucoma

The purpose of this study was to investigate the prospective association between intrinsic capacity (IC) and the risk of incident glaucoma.

We performed prospective cohort analyses among 397,881 UK Biobank participants. An IC deficit composite score was constructed based on six IC components. Cox proportional hazards models were utilized to estimate the associations of IC deficit scores and individual IC components with the risk of glaucoma. We tested gene-IC interactions using polygenic risk score (PRS) data for glaucoma.

During a median follow-up time of 13.8 years, 6264 glaucoma cases were identified, encompassing 1661 cases of primary open-angle glaucoma (POAG). After adjustments for glaucoma PRS and conventional risk factors, each 1-point increase in IC score was associated with a 12% higher glaucoma risk (hazard ratio [HR] = 1.12, 95% confidence interval [CI] = 1.09-1.14). Participants with no less than 4 IC deficits had a 65% increased risk compared with those with no deficits (HR = 1.65, 95% CI = 1.43-1.90). Evidence of interaction between IC and glaucoma PRS was observed on the multiplicative scale, whereas no significant interaction was found on the additive scale. Population attributable fraction (PAF) analysis suggested that 12.0% of glaucoma cases could be prevented if all individuals maintained optimal IC.

Impaired IC is significantly associated with an elevated risk of developing glaucoma, highlighting the value of nurturing and maintaining IC in preventing glaucoma.

Our findings suggest that assessing and maintaining IC may serve as a practical strategy for early identification and prevention of glaucoma in clinical and population health settings.