{"title":"Causal relationship between non-alcoholic fatty liver disease and sarcopenia: a bidirectional Mendelian randomization study","authors":"Meng Chen, Jili Liu, Xin Xia, Yarong Wang, Hongying Zheng","doi":"10.3389/fmed.2024.1422499","DOIUrl":null,"url":null,"abstract":"IntroductionA 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.MethodsThe study employed the two-sample MR approach to investigate the bi-directional causality between NAFLD and sarcopenia. Published summary statistics were used to obtain instrumental variables (IVs) at the genome-wide significance level.ResultsIVW analysis showed that the risk of NAFLD was reduced when walking pace was increased (OR = 0.435, 95%CI 0.240–0.789, <jats:italic>p</jats:italic> = 0.006); Increasing appendicular lean mass (ALM) decreased the risk of NAFLD (OR = 0.906, 95%CI 0.838–0.980, <jats:italic>p</jats:italic> = 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, <jats:italic>p</jats:italic> = 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, <jats:italic>p</jats:italic> = 0.001); whereas NAFLD showed no correlation with usual walking pace or grip strength (all with <jats:italic>p</jats:italic> &gt; 0.05). MR-Egger regression analysis showed that there was no horizontal pleiotropy in the SNPs (all with <jats:italic>p</jats:italic> &gt; 0.05).ConclusionThe 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.","PeriodicalId":12488,"journal":{"name":"Frontiers in Medicine","volume":null,"pages":null},"PeriodicalIF":3.1000,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fmed.2024.1422499","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
引用次数: 0
Abstract
IntroductionA 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.MethodsThe study employed the two-sample MR approach to investigate the bi-directional causality between NAFLD and sarcopenia. Published summary statistics were used to obtain instrumental variables (IVs) at the genome-wide significance level.ResultsIVW 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).ConclusionThe 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.
期刊介绍:
Frontiers in Medicine publishes rigorously peer-reviewed research linking basic research to clinical practice and patient care, as well as translating scientific advances into new therapies and diagnostic tools. Led by an outstanding Editorial Board of international experts, this multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
In addition to papers that provide a link between basic research and clinical practice, a particular emphasis is given to studies that are directly relevant to patient care. In this spirit, the journal publishes the latest research results and medical knowledge that facilitate the translation of scientific advances into new therapies or diagnostic tools. The full listing of the Specialty Sections represented by Frontiers in Medicine is as listed below. As well as the established medical disciplines, Frontiers in Medicine is launching new sections that together will facilitate
- the use of patient-reported outcomes under real world conditions
- the exploitation of big data and the use of novel information and communication tools in the assessment of new medicines
- the scientific bases for guidelines and decisions from regulatory authorities
- access to medicinal products and medical devices worldwide
- addressing the grand health challenges around the world