Lung function and nonalcoholic fatty liver disease: a Mendelian randomization study

Introduction: Associations of pulmonary function as evaluated by forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) with non-alcoholic fatty liver disease (NAFLD) have been reported in observational studies. Nevertheless, observational studies are susceptible to bias and reverse causality, making it difficult to infer the existence and direction of causality. We aimed to evaluate the causal effect of pulmonary function on NAFLD using the Mendelian randomization (MR) method. Material and methods: We performed univariate MR, multivariate MR, and bidirectional two-sample MR analyses to jointly assess the causal relationship between pulmonary function and NAFLD. In addition to the inverse variance weighting method as the primary MR analysis, three complementary methods were also performed. A series of sensitivity analyses were carried out to rule out pleiotropy. Results: We found that each genetically predicted (standard deviation) SD increase in FEV1 and FVC was associated with decreased NAFLD risk. However, after adjusting for height in the multivariate MR, only the effect of FEV1 on NAFLD risk remained significant. Furthermore, we found no causal effect of NAFLD on lung function in the reverse MR analysis. Conclusions: Our findings indicated that reduced lung function, especially FEV1, is causally associated with the risk of NAFLD. Although the mechanism remains unclear, FEV1 could be considered when assessing NAFLD risk and as a potential target for NAFLD prevention.