Lipids & metabolic liver disease
Integrative genetic and liver transcriptomic analyses identify TRIB1AL as a target for steatotic liver disease
Authors' conclusion
These results open the door to liver-targeted therapeutics silencing of the noncoding genome for the prevention and treatment of MASLD and cardiometabolic diseases.
Study context
- Population
- Genome-wide association studies (GWAS) meta-analysis of MASLD cases and controls; liver RNA sequencing and genome-wide genotyping of individuals of the Quebec Obesity Biobank; UK Biobank participants with whole-exome sequencing16,532 cases · 1,240,188 controls
- Outcome
- Liver-expressed genes linked with MASLD
Methodological detailsGWAS meta-analysis with mendelian randomization and liver transcriptomic analyses, genetic colocalization, phenome-wide mendelian randomization (MR), Liver RNA sequencing and genome-wide genotyping in 504 Quebec Obesity Biobank individuals
- GWAS meta-analysis with mendelian randomization and liver transcriptomic analyses
- Genetic colocalization
- Phenome-wide MR
- Liver RNA sequencing and genome-wide genotyping in 504 Quebec Obesity Biobank individuals
Pooled result
As reported in the abstract
- Confirmed genes previously linked with MASLD; identified novel ones incl. AKNA, EPHA2, CHEK2 and PCCB
- Strong and positive effect of lncRNA TRIB1AL on MASLD
- Lead variant not linked with expression of nearby protein-coding gene TRIB1
Further pooled results
Rare loss-of-function variants in TRIB1 (UK Biobank, whole-exome sequencing)
- Not associated with liver fat accumulation or plasma TG levels
Targeted- and phenome-wide MR of liver-expressed TRIB1AL
- Lower liver-expressed TRIB1AL associated with reduced liver fat, lower plasma lipoprotein-lipid levels and decreased atherosclerotic CVD risk
Original publication
Integrative genetic and liver transcriptomic analyses identify TRIB1AL as a target for steatotic liver disease. J Clin Endocrinol Metab. Published 4 February 2026. doi:10.
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