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ORIGINAL RESEARCH article

Front. Med.
Sec. Hepatobiliary Diseases
Volume 11 - 2024 | doi: 10.3389/fmed.2024.1422499

Causal relationship between Non-alcoholic fatty liver disease and Sarcopenia：A Bidirectional Mendelian randomization study

Provisionally accepted
Meng Chen Meng Chen 1Jili Liu Jili Liu 2Xin Xia Xin Xia 3Yarong Wang Yarong Wang 1Hongying Zheng Hongying Zheng 1*
  • 1 General Hospital of Ningxia Medical University, Yinchuan, China
  • 2 First Hospital of Shanxi Medical University, Taiyuan, Shaanxi, China
  • 3 National Clinical Research Center for Geriatric Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China

The final, formatted version of the article will be published soon.

    Introduction: A correlation between non-alcoholic fatty liver disease and sarcopenia is demonstrated, but the causality remains unclear. Our study aims to clarify the point of genetics between non-alcoholic fatty liver disease (NAFLD) and sarcopenia at the level of gene prediction through two-sample Mendelian randomization (MR) analysis.The study employed the two-sample MR approach to investigate the bidirectional causality between NAFLD and sarcopenia. Published summary statistics were used to obtain instrumental variables (IVs) at the genome-wide significance level. Results: IVW analysis showed that the risk of NAFLD was reduced when walking pace was increased (OR=0.435, 95%CI 0.240-0.789, P=0.006); Increasing appendicular lean mass(ALM) decreased the risk of NAFLD(OR=0.906, 95%CI 0.838-0.980, P=0.014); Those older than 60 were more likely to suffer from NAFLD if they had low grip strength(OR=1.411, 95%CI 1.087-1.830, P=0.0012). In the reverse MR study, weight median analysis showed that NAFLD caused a decrease in ALM (OR=0.953, 95%CI 0.957-0.994, P=0.001); whereas NAFLD showed no correlation with usual walking pace or grip strength (all with P>0.05). MR-Egger regression analysis showed that there was no horizontal pleiotropy in the SNPs (all with P>0.05). Conclusion: The characteristics related to sarcopenia (Usual walking pace, appendicular lean mass and low hand grip strength) may play a causal role in the development of nonalcoholic fatty liver disease, although the underlying mechanisms need to be further investigated. The presence of specific single nucleotide polymorphisms (SNPs) such as rs3747207, rs429358, and rs73001065 has been identified in the PNPLA3, APOE, and MAU2 proteins. These genetic markers represent potential targets for future interventions aimed at addressing, managing, or mitigating the risk of NAFLD.

    Keywords: Alcoholic fatty liver disease, Sarcopenia, Mendelian Randomization Analysis, causal relationship, Genetics

    Received: 24 Apr 2024; Accepted: 09 Sep 2024.

    Copyright: © 2024 Chen, Liu, Xia, Wang and Zheng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Hongying Zheng, General Hospital of Ningxia Medical University, Yinchuan, China

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