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. 2025 Apr 1;66(4):47.
doi: 10.1167/iovs.66.4.47.

Biological Age Acceleration, Genetic Susceptibility, and Incident Glaucoma Risk

Wei-Qi Song  1 , Wen-Fang Zhong  1 , Zhi-Hao Li  1 , Dan Liu  1 , Jiao-Jiao Ren  2 , Dong Shen  1 , Jian Gao  1 , Pei-Liang Chen  1 , Jin Yang  1 , Xiao-Meng Wang  1 , Fang-Fei You  1 , Chuan Li  1 , Huan Chen  1 , Jia-Hao Xie  1 , Chen Mao  1
Affiliations

Biological Age Acceleration, Genetic Susceptibility, and Incident Glaucoma Risk

Wei-Qi Song et al. Invest Ophthalmol Vis Sci. .

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.

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Conflict of interest statement

Disclosure: W.-Q. Song, None; W.-F. Zhong, None; Z.-H. Li, None; D. Liu, None; J.-J. Ren, None; D. Shen, None; J. Gao, None; P.-L. Chen, None; J. Yang, None; X.-M. Wang, None; F.-F. You, None; C. Li, None; H. Chen, None; J.-H. Xie, None; C. Mao, None

Figures

Figure 1.
Figure 1.
Association between biological age acceleration and incident glaucoma. (A) Klemera–Doubal method Biological Age (KDM-BA) acceleration. (B) PhenoAge acceleration. Restricted cubic spline regression model adjusted for chronological age, sex, ethnicity, education, Townsend deprivation index, body mass index, smoking status, drinking status, healthy diet, physical activity, wearing glasses, diabetes, and hypertension. CI, confidence interval; HR, hazard ratio.
Figure 2.
Figure 2.
The joint association of biological age acceleration and genetic risk in relation to risk of glaucoma. (A) Klemera–Doubal method Biological Age (KDM-BA) acceleration. (B) PhenoAge acceleration. The results were adjusted for chronological age, sex, ethnicity, education, Townsend deprivation index, body mass index, smoking status, drinking status, healthy diet, physical activity, wearing glasses, diabetes, and hypertension. CI, confidence interval; HR, hazard ratio.
Figure 3.
Figure 3.
Association of biological age acceleration with the risk of glaucoma stratified by potential risk factors. The results were adjusted for chronological age, sex, ethnicity, education, Townsend deprivation index, body mass index, smoking status, drinking status, healthy diet, physical activity, wearing glasses, diabetes, and hypertension. CI, confidence interval; HR, hazard ratio; KDM-BA, Klemera–Doubal method Biological Age.
See this image and copyright information in PMC

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