The role of cytokines as predictors for NAFLD-related diseases: A bidirectional Mendelian randomization study

Prior research has highlighted associations between inflammatory cytokines and non-alcoholic fatty liver disease (NAFLD), but causal relationships remain unclear. Employing the Mendelian randomization (MR) approach, this investigation aims to explore the connection between 41 inflammatory cytokines and NAFLD-related diseases.

Our research implemented bidirectional study focusing on 41 cytokines in 8,293 Finns, predicting genetic associations with NAFLD, nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. We primarily utilized the inverse variance weighted (IVW) method to evaluate the bidirectional relationships. Additionally, a sensitivity analysis was carried out to ensure the reliability of our findings.

An elevated risk for NAFLD was correlated with both IL-2 (OR = 1.226, 95 % CI = 1.018-1.477, p = 0.031) and TNF-β (OR = 1.151, 95 % CI = 1.011-1.310, p = 0.033). IL-16 is associated with decreased NAFLD risk (OR = 0.820, 95 % CI = 0.719-0.934, p = 0.033). β-NGF (OR = 2.495, 95 % CI = 1.019-6.108, p = 0.045) and SCGFβ (OR = 1.541, 95 % CI = 1.052-2.256, p = 0.026) are linked to higher NASH risk. No significant associations were found for fibrosis and cirrhosis. Furthermore, the causal relationship between genetic predisposition to NAFLD-related diseases and various inflammatory cytokines was established.

Our MR analysis identifies specific cytokines as genetic predictors for NAFLD and NASH. IL-2 and TNF-β increase NAFLD risk, IL-16 appears protective, and β-NGF and SCGFβ are associated with greater NASH risk. These insights are crucial for understanding the etiology and treatment of NAFLD-related diseases.