Visceral adipose tissue and risk of nonalcoholic fatty liver disease: A Mendelian randomization study
Min Tao, Guanghong Zhou, Jing Liu, Miao He, Cong Wang, Xie Luo, Lili Zhang
Abstract
OBJECTIVE: Observational studies have shown that visceral adipose tissue (VAT) can increase the risk of nonalcoholic fatty liver disease (NAFLD). However, the causality of this association remains unclear. Therefore, this study aimed to explore the causal association between VAT and NAFLD. DESIGN: We obtained single-nucleotide polymorphisms strongly associated with VAT (n = 325,153) from large-scale genome-wide association studies. Summary-level data for NAFLD (2275 cases and 375,002 controls) was available from the FinnGen consortium. We applied two-sample Mendelian randomization (MR) to determine the causal association between VAT and NAFLD. The random-effects inverse-variance weighted (IVW) method was used as the main MR approach, with alternate methods including the weighted median (WM) approach and MR-Egger regression. In addition, we conducted sensitivity analyses to assess the robustness of MR analyses. RESULTS: Genetically predicted higher VAT mass is causally associated with a higher risk of NAFLD. The three analysis results of MR were as follows: IVW (β = 0.665, odds ratio [OR] = 1.944, 95% confidence interval [CI] = 1.482-2.550, p = 1.58e-06], WM (β = 0.615, OR = 1.849, 95% CI = 1.272-2.689, p = 1.29e-03), and MR-Egger (β = 1.250, OR = 3.490, 95% CI = 1.522-7.998, p = 3.52e-03). In the sensitivity analysis, the data showed heterogeneity (p < 0.05) but no pleiotropy (p = 0.145). CONCLUSION: This study provided genetic evidence that higher VAT mass causally associated with a higher risk of NAFLD. The amount of VAT could be reduced using a therapeutic strategy for managing NAFLD.