Is There a Causal Connection? Mendelian Randomization Analysis of Muscular Dystrophies and Non-Alcoholic Fatty Liver Diseases

Abstract

Abstract Background Muscular dystrophies (MD) are a group of genetically inherited disorders characterized by progressive muscle degeneration. Prior observational studies have indicated potential, yet inconclusive, links between MD and liver conditions such as non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Despite these associations, a definitive causal relationship between MD and NAFLD has not been firmly established. Objective Our objective was to assess the potential causal relationships between of MD and liver conditions such as NAFLD and/or NASH, using the latest data available. Methods We employed a two-sample Mendelian Randomization (MR) approach, drawing on genome-wide association study (GWAS) summary statistics for MD and NAFLD/NASH. Furthermore, we performed sensitivity analyses to ensure the reliability and robustness of our findings. Results Our findings did not reveal any significant evidence supporting a causal link between MD and NAFLD (NSNP = 8, odds ratio [OR]: 0.986, 95% CI: 0. 931-1.043, P = 0.62) or NASH (NSNP = 8, odds ratio [OR]: 0.859, 95% CI: 0.692–1.066, P = 0.17). The statistical analysis indicated that the causality between MD and NAFLD/NASH was not significant (P > 0.05). Furthermore, our sensitivity analysis did not identify any significant heterogeneity or instances of horizontal pleiotropy. Conclusions The study concludes that there is no substantial evidence to suggest a causal relationship between MD and NAFLD/NASH. This finding could lead to a reevaluation of the necessity for extensive and potentially costly liver investigations in MD patients. It also suggests that other confounding factors might be at play in the previously observed associations, highlighting the need for further research in this area.