AccScience Publishing / EJMO / Online First / DOI: 10.36922/EJMO025160123
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SHORT COMMUNICATION

Causal relationships between cathepsins and psychiatric disorders: A Mendelian randomization study

Zhao Hui Yang1 ,  Ao Wang2 ,  Ke Yi1,2*
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1 Department of Orthopedics, Hubei Provincial Key Laboratory of Occurrence and Intervention of Rheumatic Diseases / Hubei Provincial Clinical Research Center for Nephrology, Minda Hospital of Hubei Minzu University, Hubei Minzu University, Enshi, Hubei, China
2 Key Laboratory of Obstetrics and Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China
EJMO, 025160123 https://doi.org/10.36922/EJMO025160123
Received: 14 April 2025 | Revised: 2 May 2025 | Accepted: 8 May 2025 | Published online: 6 June 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Introduction: Observational epidemiological studies investigating the association between cathepsins and psychiatric disorders have reported inconsistent results. Objectives: The objective of this study was to evaluate the potential causal effects of cathepsins on psychiatric disorders using Mendelian randomization (MR) analysis. Methods: A two-sample MR analysis was conducted using single-nucleotide polymorphisms as instrumental variables to examine the effects of cathepsins on psychiatric disorders. The study assessed both the individual and combined impacts of various cathepsins through univariable and multivariable MR analyses. Statistical techniques included the inverse-variance weighted method, along with supplementary approaches such as MR-egger regression, to ensure a comprehensive assessment. Results: Univariable MR analysis demonstrated a significant correlation between cathepsin G and bipolar disorder, as well as between cathepsin S and depression. In addition, multivariate MR analysis further confirmed that elevated levels of cathepsin G were significantly linked to an increased risk of bipolar disorder, while elevated levels of cathepsin S were linked to a higher risk of depression – even after adjusting for the effects of other cathepsins. Reverse MR and sensitivity analyses supported the robustness of these findings. Conclusion: This study suggests that cathepsin G and S are casually associated with an increased risk of bipolar disorder and depression, respectively. However, due to the limitations of the MR approach, including pleiotropic effects, these associations should be considered with caution.

Keywords
Causal effect
Cathepsins
Mendelian randomization
Psychiatric disorders
Risk
Funding
None.
Conflict of interest
The authors declare that they have no conflicts of interest.
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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing
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