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

Area of Science:

• Hepatology
• Public Health
• Genetics

Background:

• Causal links between behavioral factors and non-alcoholic fatty liver disease (NAFLD) risk are not fully understood.
• The potential mediating role of liver function in these associations requires further investigation.

Purpose of the Study:

• To investigate the causal associations between behavioral factors and NAFLD risk.
• To determine if liver function mediates the relationship between behavioral factors and NAFLD.

Main Methods:

• Two-sample Mendelian randomization (2SMR) and multivariable MR (MVMR) analyses were employed using summary-level genetic data.
• Linkage Disequilibrium Score Regression (LDSC) assessed genetic correlations, and NHANES data explored dose-response relationships.
• MVMR with Bayesian model averaging (MR-BMA) identified the key mediating liver function index.

Main Results:

• Leisure screen time (ST) and smoking initiation (SI) showed associations with NAFLD risk in 2SMR.
• Independent association of ST with NAFLD risk was confirmed by MVMR (β=0.334, P=4.6e-5).
• A linear dose-response relationship was observed, with risk increasing significantly after 5 hours of ST. Alanine transaminase (ALT) mediated 54% of the ST-NAFLD association.

Conclusions:

• Leisure screen time (ST) is independently associated with an elevated risk of NAFLD.
• Limiting daily screen time to under 5 hours is recommended to mitigate NAFLD risk.
• Alanine transaminase (ALT) is identified as a significant mediator in the association between ST and NAFLD.