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. 2024 Sep 12;19(9):e0310292.
doi: 10.1371/journal.pone.0310292. eCollection 2024.

Association between various cathepsins and uterine leiomyoma: A Mendelian randomization analysis

Tingxiu Liu  1   2 , Yuehan Ren  1   2 , Junning Zhang  2   3 , Hechun Yin  4 , Zheng Zheng  1 , Mingyue Zhang  1 , Yan Liao  1   2 , Liangliang Yang  1   2 , Chang Liu  1   2 , Xinmin Liu  1 , Peiyu Yan  5   6
Affiliations

Association between various cathepsins and uterine leiomyoma: A Mendelian randomization analysis

Tingxiu Liu et al. PLoS One. .

Abstract

Emerging evidence suggests a tentative association between cathepsins and uterine leiomyoma (UL). Previous investigations have predominantly focused on the role of cathepsins in the metastasis and colonization of gynecological malignancies. Still, observational studies may lead to confounding and biases. We employed a bidirectional Mendelian randomization (MR) analysis to elucidate the causative links between various cathepsins and UL. Instrumental variables (IVs) of cathepsins and UL within the European cohort were from extant genome-wide association study datasets. Sensitivity assessments was executed, and the heterogeneity of the findings was meticulously dissected to affirm the solidity of the outcomes. Our findings reveal the association between cathepsin B (CTSB) and an elevated risk of developing UL (all cancers excluded) [Inverse Variance Weighted (IVW) method]: OR = 1.06, 95%CI [1.02, 1.11], P = 0.008895711. Although the association does not persist after multiple testing or Steiger filtering, this finding adds to our understanding of the causal relationship between CTSB of various cathepsins and UL (all cancers excluded) and may herald new therapeutic avenues for individuals affected by this condition.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. The overview flowchart of hypothesis and study design.
A two-sample, bidirectional MR analysis using summary statistics from multiple genome‐wide association studies (GWAS) to investigate the association between various cathepsins and uterine leiomyoma [13].
Fig 2
Fig 2. Forest plot of multivariable bidirectional Mendelian randomization analysis [IVW method] for various cathepsins and uterine leiomyoma.
Fig 3
Fig 3. Forest plot of multivariable bidirectional Mendelian randomization analysis [IVW method] for various cathepsins and leiomyoma of uterus (all cancers excluded).
Fig 4
Fig 4. Forest plot of multivariable bidirectional Mendelian randomization analysis for cathepsin B and uterine leiomyoma (all cancers excluded).
See this image and copyright information in PMC

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