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Causal association between macrophage migration inhibitory factor and nonalcoholic fatty liver disease: A two-sample
Furong Yu1, Yonghong Fang2, Peifei Fang3
1Department of Medical Technology, Anhui Medical College, Hefei, Anhui, China.
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.
Insights
This study found macrophage migration inhibitory factor (MIF) causally linked to nonalcoholic fatty liver disease (NAFLD). Macrophage colony-stimulating factor 1 (CSF1) showed no significant association with NAFLD risk.
Area of Science:
- Hepatology
- Immunology
- Genetics
Background:
- Nonalcoholic fatty liver disease (NAFLD) is a growing health concern.
- Potential roles of macrophage colony-stimulating factor 1 (CSF1) and macrophage migration inhibitory factor (MIF) in NAFLD pathogenesis are suggested.
- Causal links between CSF1, MIF, and NAFLD require clarification.
Purpose of the Study:
- To investigate the causal associations between CSF1, MIF, and NAFLD.
- Utilize Mendelian randomization (MR) to assess genetic predispositions.
Main Methods:
- A 2-sample Mendelian randomization (MR) analysis was performed.
- Summary statistics from genome-wide association studies (GWAS) for CSF1, MIF, and NAFLD were used.
- Multiple MR methods (IVW, weighted median, etc.) and sensitivity analyses were employed.
Main Results:
- No significant causal effect of CSF1 on NAFLD risk was detected (OR=1.08, P=0.53).
- A significant causal association between higher MIF levels and increased NAFLD risk was observed (OR=1.14, P=0.03).
- Sensitivity analyses supported the robustness of these findings.
Conclusions:
- Macrophage migration inhibitory factor (MIF) plays a causal role in the development of nonalcoholic fatty liver disease (NAFLD).
- CSF1 does not appear to have a direct causal relationship with NAFLD risk.
- Further research into MIF-targeted therapies for NAFLD is warranted.
