{"title":"Association of behavioral factors, liver function and NAFLD: Bayesian Mendelian randomization.","authors":"Lei Pu, Cheng Pu, Xiaoyan Zhang","doi":"10.1186/s12986-025-00961-w","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The causal associations between behavioral factors (BFs) and the risk of non-alcoholic fatty liver disease (NAFLD), and whether liver function mediates these associations, remain unclear. Therefore, this study aimed to assess these associations.</p><p><strong>Methods: </strong>We performed two-sample Mendelian randomization (2SMR) and multivariable MR (MVMR) analysis using summary-level data to assess the associations between BFs and NAFLD. The linkage disequilibrium score regression (LDSC) was used for genetic correlation analysis. Additionally, we utilized NHANES database to assess dose-response relationships. Furthermore, we applied two-sample MVMR approach based on Bayesian model averaging (MR-BMA) to identify the most influential liver function index as a mediating factor, and performed mediation analysis.</p><p><strong>Results: </strong>2SMR results showed that leisure screen time (ST, β = 0.414, P = 5.91e-6) and smoking initiation (SI, β = 0.164, P = 0.012) were associated with NAFLD risk with no reverse causality. LDSC supported these associations (SI: rg = 0.291, P = 1.04e-8; ST: 0.518, P = 5.41e-21). However, MVMR showed that only ST was independently associated with NAFLD (β = 0.334, P = 4.6e-5). There was a linear relationship between ST and NAFLD, and NAFLD risk increased significantly after 5 h of ST. Alanine transaminase level was the most influential index (ALT, MIP = 0.452) and mediated 54% of the ST-NAFLD association.</p><p><strong>Conclusion: </strong>ST is independently associated with an increased risk of NAFLD. It is recommended to avoid more than 5 h of ST per day. ALT is the most influential liver function index associated with NAFLD and mediates the ST-NAFLD association.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":"22 1","pages":"63"},"PeriodicalIF":3.9000,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12183915/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nutrition & Metabolism","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12986-025-00961-w","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"NUTRITION & DIETETICS","Score":null,"Total":0}
引用次数: 0
Abstract
Background: The causal associations between behavioral factors (BFs) and the risk of non-alcoholic fatty liver disease (NAFLD), and whether liver function mediates these associations, remain unclear. Therefore, this study aimed to assess these associations.
Methods: We performed two-sample Mendelian randomization (2SMR) and multivariable MR (MVMR) analysis using summary-level data to assess the associations between BFs and NAFLD. The linkage disequilibrium score regression (LDSC) was used for genetic correlation analysis. Additionally, we utilized NHANES database to assess dose-response relationships. Furthermore, we applied two-sample MVMR approach based on Bayesian model averaging (MR-BMA) to identify the most influential liver function index as a mediating factor, and performed mediation analysis.
Results: 2SMR results showed that leisure screen time (ST, β = 0.414, P = 5.91e-6) and smoking initiation (SI, β = 0.164, P = 0.012) were associated with NAFLD risk with no reverse causality. LDSC supported these associations (SI: rg = 0.291, P = 1.04e-8; ST: 0.518, P = 5.41e-21). However, MVMR showed that only ST was independently associated with NAFLD (β = 0.334, P = 4.6e-5). There was a linear relationship between ST and NAFLD, and NAFLD risk increased significantly after 5 h of ST. Alanine transaminase level was the most influential index (ALT, MIP = 0.452) and mediated 54% of the ST-NAFLD association.
Conclusion: ST is independently associated with an increased risk of NAFLD. It is recommended to avoid more than 5 h of ST per day. ALT is the most influential liver function index associated with NAFLD and mediates the ST-NAFLD association.
期刊介绍:
Nutrition & Metabolism publishes studies with a clear focus on nutrition and metabolism with applications ranging from nutrition needs, exercise physiology, clinical and population studies, as well as the underlying mechanisms in these aspects.
The areas of interest for Nutrition & Metabolism encompass studies in molecular nutrition in the context of obesity, diabetes, lipedemias, metabolic syndrome and exercise physiology. Manuscripts related to molecular, cellular and human metabolism, nutrient sensing and nutrient–gene interactions are also in interest, as are submissions that have employed new and innovative strategies like metabolomics/lipidomics or other omic-based biomarkers to predict nutritional status and metabolic diseases.
Key areas we wish to encourage submissions from include:
-how diet and specific nutrients interact with genes, proteins or metabolites to influence metabolic phenotypes and disease outcomes;
-the role of epigenetic factors and the microbiome in the pathogenesis of metabolic diseases and their influence on metabolic responses to diet and food components;
-how diet and other environmental factors affect epigenetics and microbiota; the extent to which genetic and nongenetic factors modify personal metabolic responses to diet and food compositions and the mechanisms involved;
-how specific biologic networks and nutrient sensing mechanisms attribute to metabolic variability.