Ophthalmology Science (Sep 2025)

The Association between Myopia and Anxiety: A Bidirectional 2-Sample Mendelian Randomization Study

  • Waihang Wong, MD,
  • Yimin Qin, MD,
  • Chi Liu, PhD,
  • Shiran Zhang, PhD,
  • Yu Jiang, PhD,
  • Yangfa Zeng, MD,
  • Decai Wang, PhD,
  • Lingyi Liang, PhD,
  • Xiaotong Han, PhD

DOI
https://doi.org/10.1016/j.xops.2025.100832
Journal volume & issue
Vol. 5, no. 5
p. 100832

Abstract

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Objective: To investigate whether there is a causal relationship between generalized anxiety disorder (GAD) and myopia. Design: A bidirectional 2-sample Mendelian randomization (MR) analysis. Subjects: For the forward MR, 11 single nucleotide polymorphisms (SNPs) associated with GAD were obtained from the FinnGen Research (5280 cases and 368 054 controls; European). For reverse MR, 253 SNPs associated with mean spherical equivalent (MSE) were derived from the UK Biobank (95 619 participants; European). Methods: Summary-level data from the 2 genome-wide association studies were used to conduct bidirectional MR analyses. Four MR methodologies—inverse variance weighted (IVW), MR-Egger regression, weighted median, and weighted mode—were employed, with IVW serving as the primary analysis. Sensitivity analyses, including MR-Egger intercept and heterogeneity Q test, were performed. Main Outcome Measures: The outcomes of the forward and reverse MR analyses were MSE and GAD, respectively. Results: This study demonstrated a significant causal effect of GAD and myopia, suggesting individuals with GAD are at an elevated risk of more myopic MSE (IVW: β = −0.138; 95% confidence interval [CI] −0.221 to −0.056, P = 0.001). Conversely, we did not find evidence to support a causal effect of myopia on GAD (IVW: β = −0.017; 95% CI −0. 051 to −0.016, P = 0.308). Sensitivity analyses revealed no evidence of genetic confounding to bias the estimate of causal effect. Conclusions: Our study demonstrates a significant causal relationship between GAD and a more myopic MSE, though the effect size was relatively small. These findings could be taken into consideration while implementing mental health interventions in children. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

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