[Two-sample Mendelian randomization analysis for the causal relationship between 91 circulating inflammatory proteins and liver cirrhosis].

<b>Objective:</b> To analyze the causal relationship between circulating inflammatory proteins and the risk of liver cirrhosis by the two-sample Mendelian randomization (MR) method. <b>Methods:</b> 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 (<i>OR</i>) 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 <i>Q</i>-test. <b>Results:</b> 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 [<i>OR</i>(<i>CI</i>)=0.66,<i>P</i>=9.73×10^-5], interleukin-18 [<i>OR</i>(<i>CI</i>)=0.76,<i>P</i>=0.013], tumor necrosis factor ligand superfamily member 12[<i>OR</i>(<i>CI</i>)=0.75,<i>P</i>=0.024], monocyte chemoattractant protein 2 [<i>OR</i>(<i>CI</i>)=0.89,<i>P</i>=0.036], and C-C motif chemokine 25 [<i>OR</i>(<i>CI</i>)=0.84,<i>P</i>=0.039], were negatively correlated with cirrhosis and were protective factors for cirrhosis. T cell surface glycoprotein CD5 [<i>OR</i> (<i>CI</i>)=1.29,<i>P</i>=0.035] and C-X-C motif chemokine 10 [<i>OR</i>(<i>CI</i>)=1.32,<i>P</i>=0.043] were positively correlated with cirrhosis and were risk factors for cirrhosis. The results of the MR-PRESSO, <i>Q</i>-test, MR-Egger intercept test, and leave-one-out method all showed the stability. <b>Conclusion:</b> 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.