Obstet Gynecol Sci.  2025 May;68(3):237-243. 10.5468/ogs.24254.

Causal association of cathepsins with female infertility: a bidirectional Mendelian randomization analysis

• Liu L
• Liao M
• Liu B
• Huang Q
• Wu H
• Li M

• KMID: 2567920
• DOI: http://doi.org/10.5468/ogs.24254

Abstract

Objective
This study aimed to systematically evaluate potential causal relationships between nine cathepsins and female infertility using Mendelian randomization (MR) methods.
Methods
A bidirectional MR analysis was conducted utilizing single nucleotide polymorphisms as instrumental variables to investigate the potential causal effects between nine cathepsins and female infertility. Genetic data on female infertility were sourced from the FinnGen study, and cathepsin-related data were obtained from genome-wide association studies datasets of European ancestry.
Results
Elevated levels of cathepsin E were significantly and inversely associated with the risk of female infertility, suggesting a potential protective role. This finding was further supported by multivariable MR analysis. However, no significant associations were observed between the other eight cathepsins and female infertility.
Conclusion
This study represents the first systematic MR analysis to identify a potential protective effect of cathepsin E on female infertility.

Keyword

Cathepsin E; Female infertility; Mendelian randomization