Investigating the causal associations between five anthropometric indicators and nonalcoholic fatty liver disease: Mendelian randomization study

BACKGROUND Although the etiology of nonalcoholic fatty liver disease (NAFLD) has not been thoroughly understood, the emerging roles of anthropometric indicators in assessing and predicting the risk of NAFLD have been highlighted by accumulating evidence. AIM To evaluate the causal relationships between five anthropometric indicators and NAFLD employing Mendelian randomization (MR) design. METHODS The Anthropometric Consortium provided genetic exposure data for five anthropometric indicators, including hip circumference (HC), waist circumference (WC), waist-to-hip ratio (WHR), body mass index (BMI), and body fat percentage (BF). Genetic outcome data for NAFLD were obtained from the United Kingdom Biobank and FinnGen Consortium. Genome-wide significant single nucleotide polymorphisms were chosen as instrumental variables. Univariable MR (UVMR) and multivariable MR (MVMR) designs with analytical approaches, including inverse variance weighted (IVW), MR-Egger, weighted median (WM), and weighted mode methods, were used to assess the causal relationships between anthropometric indicators and NAFLD. RESULTS Causal relationships were revealed by UVMR, indicating that a higher risk of NAFLD was associated with a per-unit increase in WC [IVW: odds ratio (OR) = 2.67, 95%CI: 1.42-5.02, P = 2.25 x 10(-3)], and BF was causally associated with an increased risk of NAFLD (WM: OR = 2.23, 95%CI: 1.07-4.66, P = 0.033). The presence of causal effects of WC on the decreased risk of NAFLD was supported by MVMR after adjusting for BMI and smoking. However, no causal association between BF and NAFLD was observed. In addition, other causal relationships of HC, WHR (BMI adjusted), and BMI with the risk of NAFLD were not retained after FDR correction. CONCLUSION This study establishes a causal relationship, indicating that an increase in WC is associated with a higher risk of NAFLD. This demonstrates that a suitable decrease in WC is advantageous for preventing NAFLD.