What question did this study set out to answer?

The study aims to clarify the causal relationship between muscle mass and the risk of non-alcoholic fatty liver disease (NAFLD).

May 29, 2026Frontiers in Genetics0 citationsOpen Access

Multimodal evidence for the association between muscle mass and NAFLD: insights from hospital-based data, NHANES and mendelian randomization

WXWeidong Xie SLS X Li SHShaoliang Han

Key Points

The study aims to clarify the causal relationship between muscle mass and the risk of non-alcoholic fatty liver disease (NAFLD).
Analyzed 2,384 hospital patients with acute appendicitis using appendicular skeletal muscle mass index as a marker.
Validated findings in 21,696 NHANES participants using the United States Fatty Liver Index.
Conducted Mendelian randomization analyses with GWAS summary data.
Higher muscle mass was associated with lower NAFLD risk in hospital-based (OR = 0.16, 95% CI 0.03–0.82, P = 0.03) and NHANES populations (OR = 0.02, 95% CI 0.01–0.04, P < 0.001).
Mendelian randomization analyses indicated a potential causal inverse relationship (OR = 0.91, 95% CI 0.84–0.99, P = 0.01).
The strength of the association remained significant after controlling for BMI, cholesterol, and triglycerides (OR = 0.82, 95% CI 0.72–0.94, P = 0.003).

Abstract

Background Sarcopenia has been suggested as a potential risk factor for non-alcoholic fatty liver disease (NAFLD), but the causal relationship remains unclear. Methods We conducted a multimodal study combining hospital-based data, population survey, and Mendelian randomization (MR). A total of 2,384 patients with acute appendicitis (2016–2025) were analyzed using appendicular skeletal muscle mass index (ASMI) as a sarcopenia marker and CT-defined NAFLD as outcome. Logistic regression and SIMEX correction were applied. The association was validated in 21,696 NHANES participants (1999–2018) using the United States Fatty Liver Index (USFLI) and double-SIMEX correction. Finally, two-sample and multivariable MR were performed using GWAS summary data. Results Higher muscle mass was consistently associated with a lower NAFLD risk in hospital-based (OR = 0.16, 95% CI 0.03–0.82, P = 0.03) and NHANES populations (OR = 0.02, 95% CI 0.01–0.04, P 0.001). MR analyses suggested a potential causal inverse relationship (OR = 0.91, 95% CI 0.84–0.99, P = 0.01), independent of BMI, cholesterol, and triglycerides (OR = 0.82, 95% CI 0.72–0.94, P = 0.003). Conclusion This multimodal evidence suggested low muscle mass as a causal risk factor for NAFLD. Interventions that maintain or increase muscle mass may reduce NAFLD risk.

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