Mendelian randomization analysis explores the relationship between cathepsin and cholelithiasis
10.3760/cma.j.cn113884-20240812-00243
- VernacularTitle:组织蛋白酶与胆石症的孟德尔随机化研究
- Author:
Ping LIU
1
;
Yi DING
;
Longqing SHI
;
Qi FU
;
Yujiao YANG
Author Information
1. 苏州大学附属第三医院老年医学科，常州 213000
- Publication Type:Journal Article
- Keywords:
Mendelian randomization analysis;
Cathepsin;
Cholelithiasis
- From:
Chinese Journal of Hepatobiliary Surgery
2025;31(1):33-37
- CountryChina
- Language:Chinese
-
Abstract:
Objective:Mendelian randomization analysis (MR) was used to investigate the causal association between nine cathepsins and cholelithiasis.Methods:Single nucleotide polymorphism (SNP) sites closely associated and mutually independent with nine cathepsins and cholelithiasis were screened out from the Genome-Wide Association Study database and the FinnGen Biobank database, respectively. SNP corresponding to exposure factors were selected as instrumental variables. Two-sample bidirectional MR analysis was conducted with methods of inverse variance weighted (IVW), weighted median and MR-Egger regression. Additionally, multivariable Mendelian randomization (MVMR) was conducted to estimate the direct effect of cathepsins on cholelithiasis. Cochran's Q test, MR-PRESSO method and MR Egger regression were used to evaluate the levels of heterogeneity and pleiotropy. And the leave-one-out method was performed for the sensitivity analysis. Results:The univariable Mendelian randomization analysis results indicated that elevated cathepsin B levels increased the overall risk of cholelithiasis (IVW: OR=1.054, 95% CI: 1.025-1.083, P<0.001). The reverse MR analyses did not support a causal effect of cholelithiasis on cathepsin B (IVW: OR=0.998, 95% CI: 0.920-1.083, P=0.969). A multivariable analysis showed that elevated cathepsin B levels were still strongly associated with an increased risk of cholelithiasis (IVW: OR=1.038, 95% CI: 1.003-1.073, P=0.031). None evidence of significant pleiotropy and heterogeneity was observed, which was verified by sensitivity analysis. Conclusion:Cathepsin B may serve as a marker for cholelithiasis, and has important guiding significance in cholelithiasis treatment.
