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Background <p>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> Methods <p>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> Results <p>2SMR results showed that leisure screen time (ST, β = 0.414, <i>P</i> = 5.91e-6) and smoking initiation (SI, β = 0.164, <i>P</i> = 0.012) were associated with NAFLD risk with no reverse causality. LDSC supported these associations (SI: rg = 0.291, <i>P</i> = 1.04e-8; ST: 0.518, <i>P</i> = 5.41e-21). However, MVMR showed that only ST was independently associated with NAFLD (β = 0.334, <i>P</i> = 4.6e-5). There was a linear relationship between ST and NAFLD, and NAFLD risk increased significantly after 5&#xa0;h of ST. Alanine transaminase level was the most influential index (ALT, MIP = 0.452) and mediated 54% of the ST-NAFLD association.</p> Conclusion <p>ST is independently associated with an increased risk of NAFLD. It is recommended to avoid more than 5&#xa0;h of ST per day. ALT is the most influential liver function index associated with NAFLD and mediates the ST-NAFLD association.</p>

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Association of behavioral factors, liver function and NAFLD: Bayesian Mendelian randomization

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月23日

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  • Lei Pu,
  • Cheng Pu,
  • Xiaoyan Zhang

摘要

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.