The role relationship played by immune cells and circulating inflammatory proteins in NAFLD

Abstract Objective The mechanisms by which immune cells and inflammatory factors influence Non-Alcoholic Fatty Liver Disease (NAFLD) remain unclear. This study employs Mendelian randomization (MR) to investigate the relationship between immune cells, inflammatory factors, and NAFLD, as well as the proportion of their mutual mediation effects on NAFLD. Methods This study utilizes MR analysis, examining the causal relationship between 731 immune cell phenotypes, 91 circulating inflammatory proteins, and NAFLD. The data are sourced from publicly available data in the GWAS Catalog. The research process consists of two steps, analyzing them through the assessment of their mediating effects. To obtain reliable results, MR analysis necessitates the fulfillment of three fundamental assumptions. In the selection of instrumental variables, SNPs are screened, requiring significant associations with the exposure factors and no association with the outcomes. Statistical analyses employ methods such as IVW, WM, and MR-Egger to evaluate the causal relationship between exposure and outcomes. Sensitivity analyses are conducted, examining heterogeneity and horizontal pleiotropy. Results Ultimately, among the 731 immune cell phenotypes, 21 phenotypes are found to have a causal relationship with NAFLD, with 6 circulating inflammatory protein phenotypes playing intermediary roles. Among the 91 circulating inflammatory protein phenotypes, 7 inflammatory factor phenotypes are found to have a causal relationship with NAFLD, with 5 immune cell phenotypes playing intermediary roles. Conclusion Immune cells and circulating inflammatory proteins play a crucial role in NAFLD, and our study may provide new insights for the diagnosis and treatment of NAFLD in the future.