Abstract
Increasing evidence indicates a potential link between macrophage colony-stimulating factor 1 (CSF1) and macrophage migration inhibitory factor (MIF) with nonalcoholic fatty liver disease (NAFLD). However, the causal relationships remain unclear. This study aims to clarify the causal associations between CSF1, MIF, and NAFLD using Mendelian randomization (MR) analysis. A 2-sample MR analysis was conducted utilizing summary statistics from publicly available genome-wide association studies (GWAS) for CSF1, MIF, and NAFLD. Various MR methods, including inverse variance weighted (IVW), weighted median, weighted mode, and MR-Egger regression, were employed, alongside sensitivity tests employing the Cochran Q test and leave-one-out method. The IVW analysis showed no significant effect of CSF1 on NAFLD risk (odds ratio = 1.08, 95% confidence interval: 0.85-1.39, P = .53), supported by other methods. In contrast, a significant association between MIF levels and NAFLD risk was observed across multiple methods, with IVW indicating an odds ratio of 1.14 (95% confidence interval: 1.01-1.29, P = .03). The findings suggest a causal relationship between MIF levels and NAFLD, providing a basis for further research into MIF-mediated pathways in NAFLD, while the lack of association with CSF1 necessitates additional investigation.