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

IF 3.2 Q1 OPHTHALMOLOGY

Ophthalmology science Pub Date : 2025-05-05 DOI:10.1016/j.xops.2025.100819

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

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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 Disclosure(s)

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

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利用电子健康记录探讨近视发病年龄对多种疾病的影响

目的探讨近视发病年龄的遗传易感性是否与未来疾病的发展有关。设计来自UK Biobank的孟德尔随机全现象关联研究（MR-PheWAS）。使用从全基因组关联研究中选择的80个变异，构建了近视发病年龄的多基因风险评分（PRS）。如果参与者在2006年3月13日至2010年10月1日招募期间拥有可用的遗传信息，则符合条件。根据截至2021年4月29日的医院发作统计数据和死亡原因，将疾病结局映射到表型代码（phecodes）。方法全现象关联研究（PheWAS）的分析确定了近视发病PRS的年龄与一系列疾病结局之间可能存在的关联。Cox比例风险分析和2样本孟德尔随机化（MR）进一步证实了PRS与通过Bonferroni校正的疾病之间的关联。疾病轨迹分析探讨了儿童发病组和成人发病组的顺序模式。主要结局指标疾病结局与近视发病年龄相关。结果我们的研究人群包括31568名英国生物银行参与者，来自17种不同疾病类别的1000个独特密码被纳入分析。在Bonferroni矫正后，PheWAS发现，当使用Bonferroni阈值时，近视发病的PRS与医院诊断的近视和其他13个结果相关(所有P <；5.0 × 10−5)。使用分层PRS的Cox比例风险分析证实了11种与剂量反应效应相关的疾病。两样本MR分析进一步支持了近视患者年龄越小，视网膜脱离、白内障、玻璃体紊乱和甲状腺功能减退的风险越高，而年龄越大的近视患者患原发性闭角型青光眼的风险越高。时间分析表明，在儿童发病组和成人发病组中，近视先于上述疾病。这一数据驱动MR-PheWAS发现了一系列眼部疾病和甲状腺功能减退与近视发病年龄有关。我们的研究结果强调了治疗年轻发病的近视和管理近视相关合并症的重要性。财务披露作者在本文中讨论的任何材料中没有专有或商业利益。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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