The role of telomere length in the causal effects of immune-mediated diseases on liver fibrosis
10.3760/cma.j.cn311367-20240516-00196
- VernacularTitle:端粒长度在免疫介导性疾病对肝纤维化的因果效应中的作用
- Author:
Jing CHEN
1
;
Qingqing LIU
1
;
Xiang SHI
1
;
Yifei JI
1
;
Cuihua LU
1
Author Information
1. 南通大学附属医院消化内科 南通大学医学院，南通 226001
- Publication Type:Journal Article
- Keywords:
Liver fibrosis;
Immune-mediated diseases;
Telomere length;
Mendelian randomization analysis;
Genome-wide association study
- From:
Chinese Journal of Digestion
2025;45(1):44-49
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the role of telomere length in the causal effects of immune-mediated diseases on liver fibrosis.Methods:Genome-wide association study (GWAS) data were extracted from open GWAS (https: //gwas.mrcieu.ac.uk) for a two-sample Mendelian randomization (MR) analysis. Five immune-mediated autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, primary biliary cirrhosis, primary biliary cholangitis, and Crohn′s disease) individually and collectively were included as exposure factors, telomere length as a mediator, and liver fibrosis as the outcome. The Wald ratio and inverse variance weighted (IVW) methods were performed to assess causal effects. The MR-Egger intercept test was adopted to evaluate the level of horizontal pleiotropy. Multivariable MR was employed to quantify the proportion of the effect of immune-mediated diseases on liver fibrosis mediated by telomere length. And sensitivity analyses were performed to assess the robustness of the results.Results:The results of IVW analysis revealed that the overall category of immune-mediated diseases, rheumatoid arthritis, systemic lupus erythematosus, primary biliary cirrhosis, primary biliary cholangitis, and Crohn′s disease were causally related to the high risk of liver fibrosis, and the OR were 1.63 (95% confidence intervals (95% CI): 1.33 to 2.10), 1.28 (95% CI: 1.14 to 1.43), 1.34 (95% CI: 1.02 to 1.74), 1.36 (95% CI: 1.27 to 1.47), 1.37 (95% CI: 1.23 to 1.52), and 1.52 (95% CI: 1.15 to 2.01), respectively ( P<0.001, <0.001, =0.032, <0.001, <0.001, =0.003). Horizontal pleiotropy was detected in the association between Crohn′s disease and liver fibrosis (MR-Egger intercept test, P=0.025).The results of multivariable MR indicated that telomere length acted as a mediating factor in the causal relationship between liver fibrosis and the overall category of immune-mediated diseases, rheumatoid arthritis, systemic lupus erythematosus, primary biliary cholangitis ( OR=2.24, 95% CI: 1.41 to 3.56; OR=1.78, 95% CI: 1.03 to 3.06; OR=2.11, 95% CI: 1.31 to 3.40; OR=2.01, 95% CI: 1.06 to 3.80; P<0.001, =0.038, =0.002, =0.032, respectively ). Conclusion:The causal effects of the overall category of immune-mediated diseases, rheumatoid arthritis, systemic lupus erythematosus, and primary biliary cholangitis on liver fibrosis are mediated by telomere length.
