Abstract
PURPOSE: To evaluate the association of biological age acceleration with incident glaucoma risk and examine whether genetic predisposition modifies it. METHODS: We included 318,556 UK Biobank participants without baseline glaucoma. Biological age was calculated using the Klemera-Doubal method Biological Age (KDM-BA) and PhenoAge algorithms. Hazard ratios (HRs) and 95% confidence intervals (CIs) of the association between biological age acceleration and incident glaucoma, and their interaction with genetic risk were analyzed by Cox regression models. Mendelian randomization analyses investigated causal associations. RESULTS: After a median follow-up of 13.5 years, 6553 participants developed glaucoma. Biological age acceleration was associated with an increased glaucoma risk. Each 5-year increment in biological age acceleration was linked to higher glaucoma risk (KDM-BA acceleration: HR, 1.12, 95% CI, 1.07-1.16; PhenoAge acceleration, HR, 1.09, 95% CI, 1.06-1.13). Biologically older participants had a higher glaucoma risk than younger participants (KDM-BA acceleration, HR, 1.10, 95% CI, 1.05-1.16; PhenoAge acceleration, HR, 1.07, 95% CI, 1.02-1.13). Genetic risk modified these relationships (all P for interactions < 0.05). Biologically older participants with high genetic risk had the highest glaucoma risk (KDM-BA acceleration, HR, 2.33, 95% CI, 2.15-2.52; PhenoAge acceleration, HR, 2.21, 95% CI, 2.05-2.38). No causal relationships were found in the Mendelian randomization analysis. CONCLUSIONS: Biological age acceleration was associated with an increased glaucoma risk, and this relationship was modified by genetic risk. However, no causal relationship was established, and further research is needed to investigate the nature of the association.