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ORIGINAL RESEARCH article

Front. Med.
Sec. Ophthalmology
Volume 11 - 2024 | doi: 10.3389/fmed.2024.1431170

Vitamin D Levels and Risk of Ocular Disorders: Insights from Bidirectional and Multivariable Mendelian Randomization Analysis

Provisionally accepted
Shipei Fan Shipei Fan 1Xing-Yu Shi Xing-Yu Shi 2Xia Li Xia Li 1*Jun Li Jun Li 1*Song-Ping Yu Song-Ping Yu 1*
  • 1 Department of Ophthalmology, Lishui Municipal central hospital, Lishui, China, Lishui, Zhejiang, China, China
  • 2 Lishui Central Hospital, Lishui, Zhejiang Province, China

The final, formatted version of the article will be published soon.

    This study aimed to assess the causal relationships between vitamin D levels and ocular disorders.Methods: Independent genetic variables were obtained from genome-wide association studies (GWAS) and publicly available databases. The summary statistics for 25-hydroxyvitamin D (25(OH)D) were obtained from two large-scale GWAS studies, with sample sizes of 324,105 and 417,580 European individuals. The genetic variants of myopia, primary open angle glaucoma (POAG), anterior iridocyclitis, senile cataract, diabetic retinopathy (DR), retinal vein occlusion (RVO), wet age-related macular degeneration (WAMD) and optic neuritis were extracted from the latest release of FinnGen consortium, which contains genome data from Finnish participants. Subsquently, mendelian randomization (MR) analyses were conducted to obtain effect estimates. Additionally, we performed multivariable MR analysis and mediation analysis to validate the results.Results: In the discovery dataset, genetically predicted vitamin D concentration was found to be causally associated with an increased risk of WAMD, (odd ratio (OR) = 1.35, 95% confidence interval (CI) = 1.09-1.67, PIVW = 0.005). However, no causal effects of genetically predisposed vitamin D levels on the risk of most types of ocular disorders were observed. Reverse MR revealed no causal relationships between the ocular diseases and vitamin D concentrations. The MR analyses of the validation dataset yielded consistent results. Additionally, the causal effect of vitamin D levels on the risk of WAMD remained significant after adjusting for potential confounders in the multivariable MR analysis (OR = 1.78, 95% CI = 1.19-2.66, PIVW = 0.005).Our MR analysis results provide robust evidence of a causal relationship between genetically predicted 25(OH)D levels and an increased risk of WAMD in European population. These findings offer important insights into the management and control of ocular disorders.

    Keywords: Vitamin D, 25(OH)D, Ocular disorders, Mendelian randomization, causal relationship

    Received: 11 May 2024; Accepted: 27 Sep 2024.

    Copyright: © 2024 Fan, Shi, Li, Li and Yu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Xia Li, Department of Ophthalmology, Lishui Municipal central hospital, Lishui, China, Lishui, Zhejiang, China, China
    Jun Li, Department of Ophthalmology, Lishui Municipal central hospital, Lishui, China, Lishui, Zhejiang, China, China
    Song-Ping Yu, Department of Ophthalmology, Lishui Municipal central hospital, Lishui, China, Lishui, Zhejiang, China, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.