Genetic evidence that FGF21 signaling reduces problematic alcohol use and alcohol-related liver disease - PubMed
4 hours ago
- #alcohol-related disorders
- #FGF21
- #Mendelian randomization
- FGF21 signaling reduces problematic alcohol use (PAU) and alcohol-related liver disease (ARLD).
- Genetic evidence from GWAS data shows higher FGF21 protein levels linked to lower PAU, fewer binge episodes, and reduced ARLD risk.
- FGF21 analogs are in development for metabolic dysfunction-associated steatotic liver disease (MASLD) and show potential for treating alcohol-related disorders.
- Behavioral pathways (reduced drinking, improved diet) and increased basal metabolic rate mediate FGF21's effects.
- Hepatic FGF21 expression reduces PAU and ARLD risk more effectively than other MASLD targets like PNPLA3 or HSD17B13.
- Receptor analyses suggest a liver-brain axis involving hippocampal FGFR3 and basal ganglia KLB expression.
- Phenome-wide MR identifies 28 protective associations with higher FGF21, including gout, indicating a favorable safety profile.
- FGF21 analogs could serve as dual-action therapeutics, addressing both harmful drinking behaviors and liver injury.
- Genetic stratification may optimize patient selection for FGF21-based therapies in clinical trials.