Identification of Novel Therapeutic Targets for MAFLD Based on Bioinformatics Analysis Combined with Mendelian Randomization.

ABSTRACT: Metabolic-associated fatty liver disease (MAFLD) is a chronic liver condition with limited therapeutic options. To identify novel drug targets, we integrated bioinformatics, Mendelian randomization (MR), and colocalization analyses. Using the Gene Expression Omnibus (GEO) database, we identified differentially expressed genes and constructed protein-protein interaction (PPI) networks, pinpointing 10 hub genes. MR and colocalization analyses revealed that Ubiquitin-like with PHD and ring finger domains 1 (UHRF1) is causally associated with MAFLD and driven by the same causal variant locus, suggesting its potential as a therapeutic target. Molecular docking identified disogenin as a candidate small-molecule drug targeting UHRF1. Drug affinity responsive target stability (DARTS) assays confir

SUBMITTER: Ren J 

PROVIDER: S-EPMC11989663 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature