Exploring Effects of Age at the Onset of Myopia on Multiple Diseases Using Electronic Health Records

Xiayin Zhang; Shan Wang; Yu Huang; Yanjie Xie; Ishith Seth; Gabriella Bulloch; Chunran Lai; Yijun Hu; Xianwen Shang; Mingguang He; Zhuoting Zhu; Honghua Yu

doi:10.1016/j.xops.2025.100819

Exploring Effects of Age at the Onset of Myopia on Multiple Diseases Using Electronic Health Records

Ophthalmol Sci. 2025 May 5;5(5):100819. doi: 10.1016/j.xops.2025.100819. eCollection 2025 Sep-Oct.

Authors

Xiayin Zhang¹, Shan Wang¹, Yu Huang¹, Yanjie Xie¹, Ishith Seth², Gabriella Bulloch², Chunran Lai¹, Yijun Hu¹, Xianwen Shang³, Mingguang He³, Zhuoting Zhu^{2

4}, Honghua Yu¹

Affiliations

¹ Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
² Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia.
³ School of Optometry, The Hong Kong Polytechnic University, Hong Kong, China.
⁴ Department of Surgery (Ophthalmology), The University of Melbourne, Melbourne, Victoria, Australia.

Abstract

Purpose: To examine whether genetic predisposition to age at the onset of myopia is associated with the development of future diseases.

Design: Mendelian randomization phenome-wide association study (MR-PheWAS) from the UK Biobank.

Participants: A polygenic risk score (PRS) for age at the onset of myopia was constructed using 80 variants selected from a genome-wide association study. Participants were eligible if they had available genetic information during recruitment between March 13, 2006, and October 1, 2010. Disease outcomes were mapped to phenotype codes (phecodes) based on hospital episode statistics and causes of death up to April 29, 2021.

Methods: The analysis of phenome-wide association studies (PheWAS) identified possible associations between the age of myopia-onset PRS and a range of disease outcomes. Cox proportional hazards analysis and 2-sample Mendelian randomization (MR) further confirmed associations between PRS and diseases passing Bonferroni correction. The disease-trajectory analysis explored the sequential patterns in childhood-onset and adult-onset groups.

Main outcome measures: Disease outcomes related to age at the onset of myopia.

Results: Our study population comprised 315 568 UK Biobank participants, and 1000 unique phecodes from 17 different disease categories were included for analysis. After Bonferroni correction, PheWAS identified younger age at myopia-onset PRS was associated with hospital-diagnosed myopia and 13 other outcomes when using the Bonferroni threshold (all P < 5.0 × 10^-5). Eleven distinct disease associations with dose-response effects were confirmed using Cox proportional hazards analysis with stratified PRS. Two-sample MR analyses provided further support for the effects of younger age at myopia on higher risks of retinal detachments, cataracts, disorders of the vitreous body, and hypothyroidism, whereas older age of the onset of myopia conferred a higher risk of primary angle-closure glaucoma. Temporal analyses indicated myopia preceded the above disorders in both the childhood-onset and adult-onset groups.

Conclusions: This data-driven MR-PheWAS identified a range of ocular disorders and hypothyroidism that were related to age at the onset of myopia. Our results highlight the importance of treating younger-onset myopia and the management of myopia-related comorbidities.

Financial disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Keywords: Age at myopia onset; Mendelian randomization; Myopia-related comorbidities; Phenome-wide association study.