Non-alcoholic fatty liver disease causally affects the brain cortical structure: a Mendelian randomization study

Area of Science:

• Neuroscience
• Genetics
• Hepatology

Background:

• Non-alcoholic fatty liver disease (NAFLD) is linked to cognitive decline and neurological issues.
• The precise cause of these brain changes in NAFLD patients remains unclear.

Purpose of the Study:

• To investigate the causal relationship between NAFLD and cortical structure using Mendelian randomization.
• To determine if NAFLD genetically influences brain volume and cortical organization.

Main Methods:

• Utilized pooled genome-wide association study (GWAS) data for NAFLD and brain imaging data from the Enigma Consortium.
• Employed two-sample Mendelian randomization (MR) analysis with inverse variance weighted (IVW) as the primary method.
• Assessed heterogeneity and pleiotropy using MR-Egger, weighted median, and MR Pleiotropy RESidual Sum and Outlier.

Main Results:

• NAFLD was found to significantly reduce global cortical surface area (SA).
• Specific alterations in the cortical structure of the cerebral gyrus were observed.
• No significant pleiotropy was detected, strengthening the causal inference.

Conclusions:

• NAFLD causally influences brain cortical structures.
• This research highlights a complex and bidirectional liver-brain axis.