The causal effect of glaucoma and diabetic retinopathy: a Mendelian randomization study

Abstract Background Previous research showed that there is an important association between glaucoma and diabetic retinopathy (DR). However, the relationship has not been clarified. In this study, we attempted to evaluate it. Methods We conducted bidirectional Two-sample Mendelian randomization (MR)...

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Main Authors: Shuyun Chen, Ming Lin, Yu Hong
Format: Article
Language:English
Published: BMC 2025-03-01
Series:Diabetology & Metabolic Syndrome
Subjects:
Online Access:https://doi.org/10.1186/s13098-025-01652-5
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author Shuyun Chen
Ming Lin
Yu Hong
author_facet Shuyun Chen
Ming Lin
Yu Hong
author_sort Shuyun Chen
collection DOAJ
description Abstract Background Previous research showed that there is an important association between glaucoma and diabetic retinopathy (DR). However, the relationship has not been clarified. In this study, we attempted to evaluate it. Methods We conducted bidirectional Two-sample Mendelian randomization (MR), Multivariable Mendelian randomization (MVMR), and Mediation analysis. The Inverse-variance-weighted method was adopted as the main MR method, supplemented by MR-Egger, weighted median, weighted mode, and simple mode. Results The results of forward MR analysis suggested that glaucoma [p = 0.001, odds ratio (OR) = 1.080] and intraocular pressure (IOP) (p = 0.019, OR = 1.100) as risk factors for DR. The reverse MR found that DR was a risk factor for glaucoma (p = 0.039, OR = 1.024) and IOP (p = 0.010, OR = 1.057). The results of MVMR analysis demonstrated that glaucoma (p = 0.046, OR = 1.069) remained an independent risk factor for DR. The bidirectional relationship between glaucoma and DR is mediated by IOP, according to the results of the Two-step MR analysis. Besides, glaucoma contributed to the positive causal link that exists between IOP and DR. Conclusion The findings demonstrated a reciprocal causal link between glaucoma and DR, with a possible mediating function for IOP. Moreover, glaucoma played an important mediator of IOP as a risk factor for DR. It offers recommendations for the early prevention of both DR and glaucoma.
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spelling doaj-art-98653dc63855409794e2be1e9df36afc2025-08-20T03:05:45ZengBMCDiabetology & Metabolic Syndrome1758-59962025-03-011711810.1186/s13098-025-01652-5The causal effect of glaucoma and diabetic retinopathy: a Mendelian randomization studyShuyun Chen0Ming Lin1Yu Hong2Department of Ophthalmology, The Second Affiliated Hospital of Fujian Medical UniversityDepartment of Urology, The Second Affiliated Hospital of Fujian Medical UniversityDepartment of Ophthalmology, The Second Affiliated Hospital of Fujian Medical UniversityAbstract Background Previous research showed that there is an important association between glaucoma and diabetic retinopathy (DR). However, the relationship has not been clarified. In this study, we attempted to evaluate it. Methods We conducted bidirectional Two-sample Mendelian randomization (MR), Multivariable Mendelian randomization (MVMR), and Mediation analysis. The Inverse-variance-weighted method was adopted as the main MR method, supplemented by MR-Egger, weighted median, weighted mode, and simple mode. Results The results of forward MR analysis suggested that glaucoma [p = 0.001, odds ratio (OR) = 1.080] and intraocular pressure (IOP) (p = 0.019, OR = 1.100) as risk factors for DR. The reverse MR found that DR was a risk factor for glaucoma (p = 0.039, OR = 1.024) and IOP (p = 0.010, OR = 1.057). The results of MVMR analysis demonstrated that glaucoma (p = 0.046, OR = 1.069) remained an independent risk factor for DR. The bidirectional relationship between glaucoma and DR is mediated by IOP, according to the results of the Two-step MR analysis. Besides, glaucoma contributed to the positive causal link that exists between IOP and DR. Conclusion The findings demonstrated a reciprocal causal link between glaucoma and DR, with a possible mediating function for IOP. Moreover, glaucoma played an important mediator of IOP as a risk factor for DR. It offers recommendations for the early prevention of both DR and glaucoma.https://doi.org/10.1186/s13098-025-01652-5Diabetic retinopathyMendelian randomizationGlaucomaIntraocular pressureRetinal nerve fiber layer
spellingShingle Shuyun Chen
Ming Lin
Yu Hong
The causal effect of glaucoma and diabetic retinopathy: a Mendelian randomization study
Diabetology & Metabolic Syndrome
Diabetic retinopathy
Mendelian randomization
Glaucoma
Intraocular pressure
Retinal nerve fiber layer
title The causal effect of glaucoma and diabetic retinopathy: a Mendelian randomization study
title_full The causal effect of glaucoma and diabetic retinopathy: a Mendelian randomization study
title_fullStr The causal effect of glaucoma and diabetic retinopathy: a Mendelian randomization study
title_full_unstemmed The causal effect of glaucoma and diabetic retinopathy: a Mendelian randomization study
title_short The causal effect of glaucoma and diabetic retinopathy: a Mendelian randomization study
title_sort causal effect of glaucoma and diabetic retinopathy a mendelian randomization study
topic Diabetic retinopathy
Mendelian randomization
Glaucoma
Intraocular pressure
Retinal nerve fiber layer
url https://doi.org/10.1186/s13098-025-01652-5
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