ArticleNature communications2022
Rare loss of function variants in the hepatokine gene INHBE protect from abdominal obesity.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Discovery of obesity genes through cross-ancestry analysis.Nature communications · 2025Pooled it
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- Protein mediators of chronic kidney disease in Type 2 diabetes: A mendelian randomization study.PLoS medicine · 2026Article
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- The evolving landscape of obesity pharmacotherapy.Nature reviews. Drug discovery · 2026Review
- A Lineup for Next Anti-Obesity Medicines: Beyond Incretin-Based Pharmacotherapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- The Biobank Rare Variant consortium powers the discovery of rare genetic associations through global collaboration.medRxiv : the preprint server for health sciences · 2026Article
- Using Multi-Omics Methods to Understand Gouty Arthritis.Current rheumatology reviews · 2026Review
- Involvement of Activin E depletion in metabolic dysfunction-associated steatohepatitis.Biochemistry and biophysics reports · 2025Article
- Integrative multi-omics analysis reveals molecular signatures of central obesity in children.Pediatric research · 2025Article
- Population-scale gene-based analysis of whole-genome sequencing provides insights into metabolic health.Nature genetics · 2025Article
- A consensus guide to preclinical indirect calorimetry experiments.Nature metabolism · 2025Review
- Activin Actions in Adipocytes.The Journal of clinical endocrinology and metabolism · 2025Review
- Dietary Insulinogenic Amino Acid Restriction Improves Glucose Metabolism in a Neonatal Piglet Model.Nutrients · 2025Article
- Metabolic Stability and Targeted Delivery of Oligonucleotides: Advancing RNA Therapeutics Beyond The Liver.Journal of medicinal chemistry · 2025Review
- Trans-ancestral rare variant association study with machine learning-based phenotyping for metabolic dysfunction-associated steatotic liver disease.Genome biology · 2025Article
- Article
- Activin E is a new guardian protecting against hepatic steatosis via inhibiting lipolysis in white adipose tissue.Experimental & molecular medicine · 2025Article
Corrections and comments
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Authors and funding
18 authors at 2 institutions in 1 country.
Funding
Abstract
Identifying genetic variants associated with lower waist-to-hip ratio can reveal new therapeutic targets for abdominal obesity. We use exome sequences from 362,679 individuals to identify genes associated with waist-to-hip ratio adjusted for BMI (WHRadjBMI), a surrogate for abdominal fat that is causally linked to type 2 diabetes and coronary heart disease. Predicted loss of function (pLOF) variants in INHBE associate with lower WHRadjBMI and this association replicates in data from AMP-T2D-GENES. INHBE encodes a secreted protein, the hepatokine activin E. In vitro characterization of the most common INHBE pLOF variant in our study, indicates an in-frame deletion resulting in a 90% reduction in secreted protein levels. We detect associations with lower WHRadjBMI for variants in ACVR1C, encoding an activin receptor, further highlighting the involvement of activins in regulating fat distribution. These findings highlight activin E as a potential therapeutic target for abdominal obesity, a phenotype linked to cardiometabolic disease.
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