Genetic insights into alcohol-associated liver disease: integrative transcriptome-wide analysis identifies novel susceptibility genes.

ABSTRACT:

Background

Alcohol-associated liver disease (ALD) is a chronic condition influenced by both genetic and environmental factors. While GWAS has identified ALD-related loci (PNPLA3, MBOAT7, TM6SF2), underlying genetic mechanisms and therapeutic targets remain unclear.

Methods

This study utilized the FinnGen R12 dataset (488,982 participants) and GTEx v8 eQTL data to perform a cross-tissue transcriptome-wide association study (TWAS) using UTMOST, with single-tissue validation via FUSION. Gene-level association analysis (MAGMA), Mendelian randomization (MR), and colocalization were applied to evaluate causal links. Functional significance was assessed through GeneMANIA, drug enrichment, and molecular docking analyses.

Results

Three ALD susceptibility genes-AFF1, C4orf36, a

SUBMITTER: Wang Q 

PROVIDER: S-EPMC12351384 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature