Exploring the relationship between cathepsin and age-related macular degeneration using Mendelian randomization

PurposeAge-related macular degeneration (AMD) is the leading cause of low vision and even blindness in the elderly population worldwide. However, no studies have been conducted to analyze the causal relationship between the cathepsin family and AMD. The present study aimed to explore and analyze thi...

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Main Authors: Qiuyuan Wang, Shanjun Cai
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-11-01
Series:Frontiers in Medicine
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Online Access:https://www.frontiersin.org/articles/10.3389/fmed.2024.1460779/full
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author Qiuyuan Wang
Qiuyuan Wang
Shanjun Cai
author_facet Qiuyuan Wang
Qiuyuan Wang
Shanjun Cai
author_sort Qiuyuan Wang
collection DOAJ
description PurposeAge-related macular degeneration (AMD) is the leading cause of low vision and even blindness in the elderly population worldwide. However, no studies have been conducted to analyze the causal relationship between the cathepsin family and AMD. The present study aimed to explore and analyze this potential association using Mendelian randomization (MR).MethodsIn this study, AMD was classified into two types: exudative AMD and atrophic AMD. Inverse-variance weighting (IVW) was used as the main analysis method. The association between nine cathepsins and the two classifications of AMD were analyzed using multivariable Mendelian randomization (MVMR). Sensitivity analysis included Cochran’s Q-test and the MR-Egger intercept test.ResultsTwo-sample MR analysis showed that higher levels of cathepsin L2 were associated with a delay in the development of atrophic AMD (IVW: p = 0.017; OR = 0.885; 95% CI = 0.799–0.979). Reverse MR analysis indicated that cathepsin E levels were increased in individuals with atrophic (IVW: p = 0.023; OR = 1.058; 95% CI = 1.007–1.111) and exudative AMD (IVW: p = 0.018; OR = 1.061; 95% CI 1 = 1.010–1.115). MVMR analysis indicated a causal relationship between cathepsin G (IVW: p = 0.025; OR = 1.124; 95% CI = 1.014–1.245), cathepsin O (IVW: p = 0.043, OR = 1.158, 95% CI = 1.004–1.336), and exudative AMD after coordinating for other types of cathepsin.ConclusionThis study demonstrated a potential link between the cathepsin family and the onset of AMD. Elevated serum concentrations of cathepsin L2 may serve as a protective factor for atrophic AMD, while increased levels of serum cathepsin G and O concentrations may promote the development of exudative AMD. Besides, the development of AMD may be associated with elevated serum concentrations of cathepsin E.
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spelling doaj-art-ceebc4ed1c2f4d3aa045f9b38f944ef62025-08-20T02:12:34ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2024-11-011110.3389/fmed.2024.14607791460779Exploring the relationship between cathepsin and age-related macular degeneration using Mendelian randomizationQiuyuan Wang0Qiuyuan Wang1Shanjun Cai2Guizhou Branch of the Affiliated Hospital of Zunyi Medical University, National Clinical Research Center of the Eye Hospital of Guizhou Province, Key Laboratory of Eye Disease Characteristics of Guizhou Province, Zunyi, ChinaDepartment of Clinical Medicine, The First Clinical College, Zunyi Medical University, Zunyi, ChinaGuizhou Branch of the Affiliated Hospital of Zunyi Medical University, National Clinical Research Center of the Eye Hospital of Guizhou Province, Key Laboratory of Eye Disease Characteristics of Guizhou Province, Zunyi, ChinaPurposeAge-related macular degeneration (AMD) is the leading cause of low vision and even blindness in the elderly population worldwide. However, no studies have been conducted to analyze the causal relationship between the cathepsin family and AMD. The present study aimed to explore and analyze this potential association using Mendelian randomization (MR).MethodsIn this study, AMD was classified into two types: exudative AMD and atrophic AMD. Inverse-variance weighting (IVW) was used as the main analysis method. The association between nine cathepsins and the two classifications of AMD were analyzed using multivariable Mendelian randomization (MVMR). Sensitivity analysis included Cochran’s Q-test and the MR-Egger intercept test.ResultsTwo-sample MR analysis showed that higher levels of cathepsin L2 were associated with a delay in the development of atrophic AMD (IVW: p = 0.017; OR = 0.885; 95% CI = 0.799–0.979). Reverse MR analysis indicated that cathepsin E levels were increased in individuals with atrophic (IVW: p = 0.023; OR = 1.058; 95% CI = 1.007–1.111) and exudative AMD (IVW: p = 0.018; OR = 1.061; 95% CI 1 = 1.010–1.115). MVMR analysis indicated a causal relationship between cathepsin G (IVW: p = 0.025; OR = 1.124; 95% CI = 1.014–1.245), cathepsin O (IVW: p = 0.043, OR = 1.158, 95% CI = 1.004–1.336), and exudative AMD after coordinating for other types of cathepsin.ConclusionThis study demonstrated a potential link between the cathepsin family and the onset of AMD. Elevated serum concentrations of cathepsin L2 may serve as a protective factor for atrophic AMD, while increased levels of serum cathepsin G and O concentrations may promote the development of exudative AMD. Besides, the development of AMD may be associated with elevated serum concentrations of cathepsin E.https://www.frontiersin.org/articles/10.3389/fmed.2024.1460779/fullcathepsinsage-related macular degenerationMendelian randomizationcausal analysismultivariable Mendelian randomization
spellingShingle Qiuyuan Wang
Qiuyuan Wang
Shanjun Cai
Exploring the relationship between cathepsin and age-related macular degeneration using Mendelian randomization
Frontiers in Medicine
cathepsins
age-related macular degeneration
Mendelian randomization
causal analysis
multivariable Mendelian randomization
title Exploring the relationship between cathepsin and age-related macular degeneration using Mendelian randomization
title_full Exploring the relationship between cathepsin and age-related macular degeneration using Mendelian randomization
title_fullStr Exploring the relationship between cathepsin and age-related macular degeneration using Mendelian randomization
title_full_unstemmed Exploring the relationship between cathepsin and age-related macular degeneration using Mendelian randomization
title_short Exploring the relationship between cathepsin and age-related macular degeneration using Mendelian randomization
title_sort exploring the relationship between cathepsin and age related macular degeneration using mendelian randomization
topic cathepsins
age-related macular degeneration
Mendelian randomization
causal analysis
multivariable Mendelian randomization
url https://www.frontiersin.org/articles/10.3389/fmed.2024.1460779/full
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