Causal relationship between cathepsin H and type 1 diabetes: A Mendelian randomization study

Abstract

Introduction: Epidemiological studies investigating the relationship between cathepsins and diabetes mellitus (DM) have reported inconsistent results.

Objective: The objective of the study is to evaluate the potential causal relationship between cathepsins and DM 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 DM. Both univariable and multivariable MR analyses were employed to assess the individual and combined effects of cathepsins.

Results: Univariable MR analysis revealed a significant association between cathepsin H and an increased risk of type 1 DM using the inverse-variance weighted method (odds ratio = 1.104; 95% confidence interval = 1.065 – 1.145; p<0.001). Reverse MR analysis and sensitivity analysis supported the robustness of this finding. In the multivariable MR analysis, elevated cathepsin H levels were found to be significantly associated with an increased risk of type 1 DM (odds ratio = 1.090; 95% confidence interval = 1.048 – 1.133; p<0.001), even after adjusting for other cathepsin types. No significant associations were observed between cathepsins and the risk of type 2 DM or gestational DM.

Conclusion: The study highlights a significant causal relationship between cathepsin H and the risk of type 1 DM.

Keywords

Causal effect / Cathepsins / Diabetes mellitus / Mendelian randomization / Risk

Acknowledgements

None.

Funding

This research was supported by the Open Project of Hubei Provincial Key Laboratory of Occurrence and Intervention of Rheumatic Diseases (Project Number: OIR202302Y) and Hubei Provincial Natural Science Foundation Joint Fund for Innovative Development (Project Number: 2024AFD070).

Conflict of interest

The authors declare that they have no competing interests.

Author contributions

Conceptualization: Rui Jin Ran, Ao Wang

Investigation: Rui Jin Ran, Ao Wang

Methodology: Rui Jin Ran, Ke Yi

Formal analysis: Ao Wang, Ke Yi

Writing–original draft: Rui Jin Ran, Ao Wang

Writing–review & editing: Rui Jin Ran, Ke Yi

Ethics approval and consent to participate

This study involves human participants; however, it utilized GWAS summary statistics obtained from previously published studies. Ethical approval for the GWAS data was granted in the original studies where all participants gave informed consent before joining the study and the National Research Ethics Service approved this study (11/EE/0538). As this research utilized secondary data, no additional informed consent was required.

Consent for publication

This study is a MR analysis based on previously published data. All data used were obtained from studies in which participants had provided informed consent before their enrollment.

Availability of data

Data are available from the corresponding author upon reasonable request.

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