ArticleNature genetics2014
Exome-wide association study identifies a TM6SF2 variant that confers susceptibility to nonalcoholic fatty liver disease.
Article in Nature genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 671 papers, 5 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
The Role of the PNPLA3, TM6SF2 and MBOAT7 Genetic Variants in the Response to Silybin-phospholipid Complex, Vitamin D and Vitamin E Based Therapy for Non-alcoholic Fatty Liver Disease Patients
Combining Gene Variants to Improve Risk Prediction for Metabolic (Dysfunction)- Associated Fatty Liver Disease and Its Progression to Cirrhosis in Indian Individuals With Type 2 Diabetes: a Cross-sectional Study
Who cites it
671 citing papers in PubMed, 5 syntheses or guidelines pooled it, 1,181 citations in OpenAlex.
- Integrative genetic and liver transcriptomic analyses identify TRIB1AL as a target for steatotic liver disease.The Journal of clinical endocrinology and metabolism · 2026Pooled it
- Meta-Analysis of Genetic Variants Associated With HBV Infection Susceptibility and Hepatocellular Carcinoma Risk.Journal of viral hepatitis · 2026Pooled it
- Meta-Analysis: Effects of Steatotic Liver Disease-Associated Genetic Risk Alleles on Longitudinal Outcomes.Alimentary pharmacology & therapeutics · 2025Pooled it
- Progress and hotspot of diet or exercise therapy in the treatment of non-alcoholic fatty liver disease.Frontiers in nutrition · 2024Pooled it
- Genome-wide association meta-analysis identifies 17 loci associated with nonalcoholic fatty liver disease.Nature genetics · 2023Pooled it
- Increased Genetic Risk for β-Cell Failure Is Associated With β-Cell Function Decline in People With Prediabetes.Diabetes · 2024Trial
- siRNA therapeutics for metabolic dysfunction-associated Steatohepatitis: Targets, delivery, clinical evidence, and translational challenges.Biochemistry and biophysics reports · 2026Review
- MASLD, diabetes and PMOS across the female life stages.Diabetologia · 2026Review
- Age-Specific Associations of Polygenic Risk Scores With Advanced Fibrosis and Histological Activity in Biopsy-Proven MASLD.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- Genetics of MASLD: a diabetes perspective.Diabetologia · 2026Review
- Hypocholesterolemia in liver and cardiovascular disease: Friend or foe?Journal of internal medicine · 2026Review
- The convergent roles of metabolic dysfunction, alcohol, and iron in steatotic liver disease: a review.Bioscience reports · 2026Review
- Comorbid Cardiovascular-Liver Disease Disparities: Current Understanding and Future Directions.Current cardiology reports · 2026Review
- The global burden of metabolic and alcohol-associated liver disease (MetALD).Hepatology communications · 2026Review
- Omics-based Decoding of Metabolic Dysfunction-associated Fatty Liver Disease: From Pathogenesis to Clinical Translation.Journal of clinical and translational hepatology · 2026Review
- Genetic and genomic insights across the steatotic liver disease spectrum.Clinical and molecular hepatology · 2026Review
- Molecular mechanisms and pathogenesis of MASH.Nature · 2026Review
- Review
- The Emerging Challenge of Non-Cirrhotic MASLD-Related Hepatocellular Carcinoma: Etiology, Immunopathology, and Precision Oncology.Liver cancer · 2026Review
- TM6SF2 overexpression suppresses the proliferation and promotes apoptosis of human hepatocellular carcinoma cells.Oncology reports · 2026Article
611 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 6 institutions in 2 countries.
Funding
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common form of liver disease. To elucidate the molecular basis of NAFLD, we performed an exome-wide association study of liver fat content. Three variants were associated with higher liver fat levels at the exome-wide significance level of 3.6 × 10(-7): two in PNPLA3, an established locus for NAFLD, and one (encoding p.Glu167Lys) in TM6SF2, a gene of unknown function. The TM6SF2 variant encoding p.Glu167Lys was also associated with higher circulating levels of alanine transaminase, a marker of liver injury, and with lower levels of low-density lipoprotein-cholesterol (LDL-C), triglycerides and alkaline phosphatase in 3 independent populations (n > 80,000). When recombinant protein was expressed in cultured hepatocytes, 50% less Glu167Lys TM6SF2 protein was produced relative to wild-type TM6SF2. Adeno-associated virus-mediated short hairpin RNA knockdown of Tm6sf2 in mice increased liver triglyceride content by threefold and decreased very-low-density lipoprotein (VLDL) secretion by 50%. Taken together, these data indicate that TM6SF2 activity is required for normal VLDL secretion and that impaired TM6SF2 function causally contributes to NAFLD.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.