June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Exploring causal effects of age at myopia onset on multiple diseases using electronic health records: a phenome-wide and polygenic risk study
Author Affiliations & Notes
  • Xiayin Zhang
    Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
  • Huang Yu
    Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
  • Yanjie Xie
    Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
  • Xianwen Shang
    Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
  • Shunming Liu
    Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
  • Zhuoting Zhu
    Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
    Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Australian Capital Territory, Australia
  • Honghua Yu
    Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
    Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, China
  • Footnotes
    Commercial Relationships   Xiayin Zhang None; Huang Yu None; Yanjie Xie None; Xianwen Shang None; Shunming Liu None; Zhuoting Zhu None; Honghua Yu None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 828. doi:
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      Xiayin Zhang, Huang Yu, Yanjie Xie, Xianwen Shang, Shunming Liu, Zhuoting Zhu, Honghua Yu; Exploring causal effects of age at myopia onset on multiple diseases using electronic health records: a phenome-wide and polygenic risk study. Invest. Ophthalmol. Vis. Sci. 2023;64(8):828.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Age at myopia onset is associated with risks of high myopia and help to distinguish genetic from acquired forms. However, its casual effects on other health-related traits are unknown. In this hypothesis-free, Mendelian randomization phenome-wide association study (MR-pheWAS), we sought to assess possible causal effects of age at myopia onset on multiple disease outcomes.

Methods : We used genome-wide data from UK Biobank to construct polygenic risk scores (PRS) of 80 variants related to age at myopia onset. Disease outcomes were mapped to phenotype codes (phecodes). We did a PheWAS to analyze possible associations between age at myopia PRS and a range of disease outcomes. Disease associations passing corrections for multiple testing were validated using Cox proportional hazards analysis and two-sample MR. Disease-trajectory analyses were conducted to explore sequential patterns between different age groups of myopia onset.

Results : Our study comprised 362,821 participants with 1040 unique phecodes from 17 different disease categories. After Bonferroni correction, PheWAS identified age at myopia PRS was associated with hospital-diagnosed myopia and 11 other outcomes; 9 distinct disease associations were supported by Cox proportional hazards analysis in dose-response manners. MR analyses provided support for causal effects of age at myopia onset on ocular disorders (Retinal detachments:OR=0.54, 95%CI=0.47-0.62; Cataracts:OR=0.79, 95%CI=0.73-0.85; Primary angle-closure glaucoma:OR=2.46, 95%CI=1.86-3.25; Disorders of the vitreous body:OR=0.74, 95%CI=0.56-0.96) and the endocrine disorder hypothyroidism (OR=0.55, 95%CI=0.34-0.89). Temporal analyses of time-at-first-diagnosis indicated that myopia preceded other ocular disorders and hypothyroidism in both childhood- and adult-onset groups.

Conclusions : Our data-driven approach identified a range of ocular disorders and hypothyroidism possibly affected by age at myopia onset, and highlighted the importance of identifying which population would benefit most from effective management of myopia-related comorbidities.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

 

Figure 1.(A)Manhattan plot showing the phenome-wide association between age at myopia PRS and disease outcomes;(B)Cox proportional hazards analysis of age at myopia PRS;(C)Two-sample MR analysis for the genetic effects of age at myopia onset on multiple diseases.

Figure 1.(A)Manhattan plot showing the phenome-wide association between age at myopia PRS and disease outcomes;(B)Cox proportional hazards analysis of age at myopia PRS;(C)Two-sample MR analysis for the genetic effects of age at myopia onset on multiple diseases.

 

Figure 2.Temporal order of diagnoses.

Figure 2.Temporal order of diagnoses.

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