ArticleFrontiers in genetics2026
Multimodal evidence for the association between muscle mass and NAFLD: insights from hospital-based data, NHANES and mendelian randomization.
Article in Frontiers in genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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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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