Two-sample Mendelian randomization analysis for the causal relationship between 91 circulating inflammatory proteins and liver cirrhosis
10.3760/cma.j.cn501113-20241024-00555
- VernacularTitle:两样本孟德尔随机化分析91种循环炎症蛋白与肝硬化的因果关系
- Author:
Mao LI
1
;
Shijun ZHOU
1
;
Li QIANG
1
;
Min CHEN
1
;
Yu TANG
1
;
Gang WU
1
Author Information
1. 西南医科大学附属医院感染科，泸州 646000
- Publication Type:Journal Article
- Keywords:
Liver cirrhosis;
Diagnosis;
Plasma inflammatory protein;
Mendelian randomization;
Genome-wide association studies
- From:
Chinese Journal of Hepatology
2025;33(6):577-586
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analyze the causal relationship between circulating inflammatory proteins and the risk of liver cirrhosis by the two-sample Mendelian randomization (MR) method.Methods:Single nucleotide polymorphisms (SNP) strongly associated with 91 plasma inflammatory proteins in genome-wide association studies (GWAS) were used as instrumental variables, and liver cirrhosis was used as the outcome variable. Random-effects inverse variance-weighted (IVW), MR Egger regression, odds ratio ( OR) and its 95% confidence interval were used to evaluate the causal relationship. Simultaneously, sensitivity analysis was performed using MR pleiotropy residuals and outliers (MR-PRESSO) and the Q-test. Results:The causal relationship between the expression of seven specific circulating inflammatory proteins and liver cirrhosis was confirmed by the inverse variance-weighted (IVW) method. The results showed that five plasma inflammatory proteins, including leukemia inhibitory factor [ OR( CI)=0.66, P=9.73×10 -5], interleukin-18 [ OR( CI)=0.76, P=0.013], tumor necrosis factor ligand superfamily member 12[ OR( CI)=0.75, P=0.024], monocyte chemoattractant protein 2 [ OR( CI)=0.89, P=0.036], and C-C motif chemokine 25 [ OR( CI)=0.84, P=0.039], were negatively correlated with cirrhosis and were protective factors for cirrhosis. T cell surface glycoprotein CD5 [ OR ( CI)=1.29, P=0.035] and C-X-C motif chemokine 10 [ OR( CI)=1.32, P=0.043] were positively correlated with cirrhosis and were risk factors for cirrhosis. The results of the MR-PRESSO, Q-test, MR-Egger intercept test, and leave-one-out method all showed the stability. Conclusion:The research results indicated that the increased levels of leukemia inhibitory factor, interleukin-18, tumor necrosis factor ligand superfamily member 12, monocyte chemoattractant protein-2, and C-C motif chemokine 25 were protective factors in the development of cirrhosis, while the increased levels of T cell surface glycoprotein CD5 and C-X-C motif chemokine 10 were risk factors for the development of cirrhosis based on genetic data.
