ArticleNature communications2022
Multiancestry exome sequencing reveals INHBE mutations associated with favorable fat distribution and protection from diabetes.
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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 39 papers.
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39citing papers in PubMed
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Who cites it
39 citing papers in PubMed, 52 citations in OpenAlex.
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- Humans with function-disrupting variants in the myostatin gene (MSTN) have increased skeletal muscle mass and strength, and less adiposity.Nature communications · 2026Article
- M-cadherin regulates the formation of adherens junctions and secondary myofibers during fetal myogenesis to determine adult myofiber number and muscle mass.Stem cell reports · 2026Article
- Involvement of Activin E depletion in metabolic dysfunction-associated steatohepatitis.Biochemistry and biophysics reports · 2025Article
- Genetic subtyping of obesity reveals biological insights into the uncoupling of adiposity from its cardiometabolic comorbidities.Nature medicine · 2025Article
- Combining evidence from human genetic and functional screens to identify pathways altering obesity and fat distribution.American journal of human genetics · 2025Article
- Associations of abdominal obesity-related dietary patterns with prediabetes and type 2 diabetes: exploring the mediating effects of body composition and altitude in Tibetan adults.Public health nutrition · 2025Article
- Activin Actions in Adipocytes.The Journal of clinical endocrinology and metabolism · 2025Review
- Mechanistic insights into Y-Box binding protein-1 mediated regulation of lipid metabolism and oxidative stress in NAFLD via INHBE/TNF-β pathway.Biomolecules & biomedicine · 2025Article
- Trans-ancestral rare variant association study with machine learning-based phenotyping for metabolic dysfunction-associated steatotic liver disease.Genome biology · 2025Article
- Activin E is a new guardian protecting against hepatic steatosis via inhibiting lipolysis in white adipose tissue.Experimental & molecular medicine · 2025Article
- Rare variant associations with birth weight identify genes involved in adipose tissue regulation, placental function and insulin-like growth factor signalling.Nature communications · 2025Article
- Molecular Docking, Pharmacophore Modeling and ADMET Prediction of Novel Heterocyclic Leads as Glucokinase Activators.Anti-inflammatory & anti-allergy agents in medicinal chemistry · 2025Article
- Transcriptomic Analysis Reveals the Potential Mechanism ofInternational journal of molecular sciences · 2024Article
- Article
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Authors and funding
62 authors at 8 institutions in 5 countries.
Parsa Akbari *Regeneron Genetics Center, Regeneron Pharmaceuticals Inc, Tarrytown, NY, USA.
Olukayode A Sosina *Regeneron Genetics Center, Regeneron Pharmaceuticals Inc, Tarrytown, NY, USA.ORCID 0000-0003-2120-0338
Jonas Bovijn *Regeneron Genetics Center, Regeneron Pharmaceuticals Inc, Tarrytown, NY, USA.
Karl LandheerRegeneron Pharmaceuticals Inc, Tarrytown, NY, USA.ORCID 0000-0001-5012-3007
Jonas B NielsenRegeneron Genetics Center, Regeneron Pharmaceuticals Inc, Tarrytown, NY, USA.
Minhee KimRegeneron Genetics Center, Regeneron Pharmaceuticals Inc, Tarrytown, NY, USA.
Senem AykulRegeneron Genetics Center, Regeneron Pharmaceuticals Inc, Tarrytown, NY, USA.ORCID 0000-0001-7250-2913
Tanima DeRegeneron Genetics Center, Regeneron Pharmaceuticals Inc, Tarrytown, NY, USA.
Mary E HaasRegeneron Genetics Center, Regeneron Pharmaceuticals Inc, Tarrytown, NY, USA.ORCID 0000-0002-2816-9268
George HindyRegeneron Genetics Center, Regeneron Pharmaceuticals Inc, Tarrytown, NY, USA.
Nan LinRegeneron Genetics Center, Regeneron Pharmaceuticals Inc, Tarrytown, NY, USA.
Ian R DinsmoreDepartment of Molecular and Functional Genomics, Geisinger Health System, Danville, PA, USA.
Jonathan Z LuoDepartment of Molecular and Functional Genomics, Geisinger Health System, Danville, PA, USA.
Stefanie HectorsRegeneron Pharmaceuticals Inc, Tarrytown, NY, USA.
Benjamin GeraghtyRegeneron Genetics Center, Regeneron Pharmaceuticals Inc, Tarrytown, NY, USA.
Mary GerminoRegeneron Pharmaceuticals Inc, Tarrytown, NY, USA.
Lampros PanagisRegeneron Pharmaceuticals Inc, Tarrytown, NY, USA.
Prodromos ParasoglouRegeneron Pharmaceuticals Inc, Tarrytown, NY, USA.
Johnathon R WallsRegeneron Pharmaceuticals Inc, Tarrytown, NY, USA.
Gabor HalaszRegeneron Pharmaceuticals Inc, Tarrytown, NY, USA.
Gurinder S AtwalRegeneron Pharmaceuticals Inc, Tarrytown, NY, USA.
Regeneron Genetics Center
DiscovEHR Collaboration
Marcus JonesRegeneron Genetics Center, Regeneron Pharmaceuticals Inc, Tarrytown, NY, USA.
Michelle G LeBlancRegeneron Genetics Center, Regeneron Pharmaceuticals Inc, Tarrytown, NY, USA.
Christopher D StillGeisinger Obesity Institute, Geisinger Health System, Danville, PA, USA.
David J CareyGeisinger Obesity Institute, Geisinger Health System, Danville, PA, USA.
Alice GiontellaDepartment of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
Marju Orho-MelanderDepartment of Clinical Sciences Malmö, Lund University, Malmö, Sweden.ORCID 0000-0002-3578-2503
Jaime BerumenUnidad de Medicina Experimental de la Facultad de Medicina de la Universidad Nacional Autónoma de México, Mexico City, Mexico.ORCID 0000-0001-6707-3317
Pablo Kuri-MoralesUnidad de Medicina Experimental de la Facultad de Medicina de la Universidad Nacional Autónoma de México, Mexico City, Mexico.
Jesus Alegre-DíazUnidad de Medicina Experimental de la Facultad de Medicina de la Universidad Nacional Autónoma de México, Mexico City, Mexico.ORCID 0000-0001-9390-3871
Jason M TorresMRC Population Health Research Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
Jonathan R EmbersonMRC Population Health Research Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.ORCID 0000-0001-7792-9422
Rory CollinsClinical Trial Service Unit & Epidemiological Studies Unit Nuffield Department of Population Health, University of Oxford, Oxford, UK.
Daniel J RaderDepartment of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-9245-9876
Brian ZambrowiczRegeneron Pharmaceuticals Inc, Tarrytown, NY, USA.ORCID 0000-0001-8831-0406
Andrew J MurphyRegeneron Pharmaceuticals Inc, Tarrytown, NY, USA.ORCID 0000-0003-4152-4081
Suganthi BalasubramanianRegeneron Genetics Center, Regeneron Pharmaceuticals Inc, Tarrytown, NY, USA.
John D OvertonRegeneron Genetics Center, Regeneron Pharmaceuticals Inc, Tarrytown, NY, USA.
Jeffrey G ReidRegeneron Genetics Center, Regeneron Pharmaceuticals Inc, Tarrytown, NY, USA.ORCID 0000-0001-8645-4713
Alan R ShuldinerRegeneron Genetics Center, Regeneron Pharmaceuticals Inc, Tarrytown, NY, USA.ORCID 0000-0001-9921-4305
Michael CantorRegeneron Genetics Center, Regeneron Pharmaceuticals Inc, Tarrytown, NY, USA.
Goncalo R AbecasisRegeneron Genetics Center, Regeneron Pharmaceuticals Inc, Tarrytown, NY, USA.ORCID 0000-0003-1509-1825
Manuel A R FerreiraRegeneron Genetics Center, Regeneron Pharmaceuticals Inc, Tarrytown, NY, USA.ORCID 0000-0001-9059-1825
Mark W SleemanRegeneron Pharmaceuticals Inc, Tarrytown, NY, USA.
Viktoria GusarovaRegeneron Pharmaceuticals Inc, Tarrytown, NY, USA.
Judith AltarejosRegeneron Pharmaceuticals Inc, Tarrytown, NY, USA.
Charles HarrisRegeneron Pharmaceuticals Inc, Tarrytown, NY, USA.
Aris N EconomidesRegeneron Genetics Center, Regeneron Pharmaceuticals Inc, Tarrytown, NY, USA.ORCID 0000-0002-6508-8942
Vincent IdoneRegeneron Pharmaceuticals Inc, Tarrytown, NY, USA.
Katia KaralisRegeneron Genetics Center, Regeneron Pharmaceuticals Inc, Tarrytown, NY, USA.
Giusy Della GattaRegeneron Genetics Center, Regeneron Pharmaceuticals Inc, Tarrytown, NY, USA.
Tooraj MirshahiGeisinger Obesity Institute, Geisinger Health System, Danville, PA, USA.ORCID 0000-0002-0754-3820
George D YancopoulosRegeneron Pharmaceuticals Inc, Tarrytown, NY, USA.
Olle MelanderDepartment of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
Jonathan MarchiniRegeneron Genetics Center, Regeneron Pharmaceuticals Inc, Tarrytown, NY, USA.ORCID 0000-0003-0610-8322
Roberto Tapia-Conyer *Instituto Tecnológico y de Estudios Superiores de Monterrey, Monterrey, Mexico.ORCID 0000-0003-3814-2904
Adam E Locke *Regeneron Genetics Center, Regeneron Pharmaceuticals Inc, Tarrytown, NY, USA.ORCID 0000-0001-6227-198X
Aris Baras *Regeneron Genetics Center, Regeneron Pharmaceuticals Inc, Tarrytown, NY, USA. aris.baras@regeneron.com.ORCID 0000-0002-6830-3396
Niek Verweij *Regeneron Genetics Center, Regeneron Pharmaceuticals Inc, Tarrytown, NY, USA.
Luca A Lotta *Regeneron Genetics Center, Regeneron Pharmaceuticals Inc, Tarrytown, NY, USA. luca.lotta@regeneron.com.ORCID 0000-0002-2619-5956
Regeneron (United States) · USGeisinger Health System · USUniversidad Nacional Autónoma de México · MXUniversity of Oxford · GBLund University · SETecnológico de Monterrey · MXUniversity of Pennsylvania · USUniversity of Verona · IT
Funding
British Heart Foundation CH/1996001/9454Cancer Research UKMedical Research Council G0300622Medical Research Council MC_EX_G0801669Medical Research Council MC_PC_12027Medical Research Council MC_PC_12028Medical Research Council MC_PC_12029Medical Research Council MC_U137686854Medical Research Council MC_UU_00017/2Medical Research Council MC_UU_00017/3Wellcome Trust
Abstract
Body fat distribution is a major, heritable risk factor for cardiometabolic disease, independent of overall adiposity. Using exome-sequencing in 618,375 individuals (including 160,058 non-Europeans) from the UK, Sweden and Mexico, we identify 16 genes associated with fat distribution at exome-wide significance. We show 6-fold larger effect for fat-distribution associated rare coding variants compared with fine-mapped common alleles, enrichment for genes expressed in adipose tissue and causal genes for partial lipodystrophies, and evidence of sex-dimorphism. We describe an association with favorable fat distribution (p = 1.8 × 10
Indexed as
Diabetes Mellitus, Type 2Adipose TissueAdiposityExomeHumansInhibin-beta SubunitsMutationINHBE protein, humanInhibin-beta Subunits
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