ArticleNature genetics2019
Human pancreatic islet three-dimensional chromatin architecture provides insights into the genetics of type 2 diabetes.
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Article in Nature genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 178 papers, 4 of them syntheses that pooled it.
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178citing papers in PubMed, 4 pooled it
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Who cites it
178 citing papers in PubMed, 4 syntheses or guidelines pooled it, 299 citations in OpenAlex.
- Rare variant analyses in 51,256 type 2 diabetes cases and 370,487 controls reveal the pathogenicity spectrum of monogenic diabetes genes.Nature genetics · 2024Pooled it
- Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation.Nature genetics · 2022Pooled it
- Multi-ethnic GWAS and fine-mapping of glycaemic traits identify novel loci in the PAGE Study.Diabetologia · 2022Pooled it
- TIGER: The gene expression regulatory variation landscape of human pancreatic islets.Cell reports · 2021Pooled it
- Nardilysin regulatesBiochemistry and biophysics reports · 2026Article
- Epigenetics in development, disease, and therapy: from mechanisms to clinical interventions.Science China. Life sciences · 2026Review
- Decoding 3D chromatin architecture reveals distinct enhancer classes underlying hierarchical gene regulation in prostate cancer.Genome biology · 2026Article
- MiRNAs in hyperglycemia-induced metabolic memory: established mechanisms and emerging nuclear activation concepts.Diabetology & metabolic syndrome · 2026Review
- Pancreatic islet α cell function and proliferation require the arginine transporter SLC7A2.The Journal of clinical investigation · 2026Article
- Crossing paths: historical and philosophical perspectives on cancer and diabetes classifications.History and philosophy of the life sciences · 2026Article
- Epigenetic landscapes in human pancreatic islets reveal distinct drivers for adaptation to age and type 2 diabetes.Nature communications · 2026Article
- Bone Organoids: A Novel Tool for Modeling and Managing Skeletal Disorders in Diabetes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- The insertion of an ATTTC repeat in an Alu element hyperactivates a neurodevelopmental enhancer in spinocerebellar ataxia type 37.Cell reports · 2026Article
- Beta cell-derived cholecystokinin drives obesity-associated pancreatic adenocarcinoma development.Nature communications · 2026Article
- 3D-super-enhancers are condensate-associated cis-regulatory communities.Nucleic acids research · 2026Article
- Combining functional annotation and multi-trait fine-mapping methods improves fine-mapping resolution at glycaemic trait loci.Human molecular genetics · 2026Article
- In vivo functional profiling and structural characterization of the humanScience advances · 2026Article
- Predictive prioritization of enhancers associated with pancreatic disease risk.Cell genomics · 2026Article
- eVLP-Mediated Cas9 Delivery for Preventing IBMIR in Islet Transplantation.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Identification of novel type 1 and type 2 diabetes genes by co-localization of human islet eQTL and GWAS variants with colocRedRibbon.Cell genomics · 2025Article
118 more citing papers are in PubMed but not listed here.
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Authors and funding
36 authors at 19 institutions in 9 countries.
Irene Miguel-EscaladaSection of Epigenomics and Disease, Department of Medicine, and National Institute for Health Research Imperial Biomedical Research Centre, Imperial College London, London, UK.
Silvia Bonàs-GuarchSection of Epigenomics and Disease, Department of Medicine, and National Institute for Health Research Imperial Biomedical Research Centre, Imperial College London, London, UK.
Inês CebolaSection of Epigenomics and Disease, Department of Medicine, and National Institute for Health Research Imperial Biomedical Research Centre, Imperial College London, London, UK.ORCID http://orcid.org/0000-0003-3528-4982
Joan Ponsa-CobasSection of Epigenomics and Disease, Department of Medicine, and National Institute for Health Research Imperial Biomedical Research Centre, Imperial College London, London, UK.ORCID http://orcid.org/0000-0002-3230-8742
Julen Mendieta-EstebanCNAG-CRG, Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain.ORCID http://orcid.org/0000-0002-5834-7643
Goutham AtlaSection of Epigenomics and Disease, Department of Medicine, and National Institute for Health Research Imperial Biomedical Research Centre, Imperial College London, London, UK.
Biola M JavierreNuclear Dynamics Programme, The Babraham Institute, Cambridge, UK.
Delphine M Y RolandoSection of Epigenomics and Disease, Department of Medicine, and National Institute for Health Research Imperial Biomedical Research Centre, Imperial College London, London, UK.
Irene FarabellaCNAG-CRG, Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain.ORCID http://orcid.org/0000-0002-7473-6227
Claire C MorganSection of Epigenomics and Disease, Department of Medicine, and National Institute for Health Research Imperial Biomedical Research Centre, Imperial College London, London, UK.
Javier García-HurtadoRegulatory Genomics and Diabetes, Centre for Genomic Regulation, The Barcelona Institute of Science and Technology, Barcelona, Spain.
Anthony BeucherSection of Epigenomics and Disease, Department of Medicine, and National Institute for Health Research Imperial Biomedical Research Centre, Imperial College London, London, UK.
Ignasi MoránSection of Epigenomics and Disease, Department of Medicine, and National Institute for Health Research Imperial Biomedical Research Centre, Imperial College London, London, UK.ORCID http://orcid.org/0000-0002-3307-7106
Lorenzo PasqualiCIBER de Diabetes y Enfermedades Metabólicas Asociadas, Madrid, Spain.ORCID http://orcid.org/0000-0003-2423-1826
Mireia Ramos-RodríguezEndocrine Regulatory Genomics Laboratory, Germans Trias i Pujol University Hospital and Research Institute, Barcelona, Spain.
Emil V R AppelNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID http://orcid.org/0000-0001-7704-6611
Allan LinnebergCenter for Clinical Research and Disease Prevention, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.ORCID http://orcid.org/0000-0002-0994-0184
Anette P GjesingNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Daniel R WitteDepartment of Public Health, Aarhus University, Aarhus, Denmark.
Oluf PedersenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID http://orcid.org/0000-0002-3321-3972
Niels GrarupNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID http://orcid.org/0000-0001-5526-1070
Philippe RavassardUniversité Sorbonne, UPMC Univ Paris 06, Inserm, CNRS, Institut du cerveau et de la moelle-Hôpital Pitié-Salpêtrière, Boulevard de l'Hôpital, Paris, France.ORCID http://orcid.org/0000-0002-0393-9262
David TorrentsBarcelona Supercomputing Center, Joint BSC-CRG-IRB Research Program in Computational Biology, Barcelona, Spain.
Josep M MercaderBarcelona Supercomputing Center, Joint BSC-CRG-IRB Research Program in Computational Biology, Barcelona, Spain.ORCID http://orcid.org/0000-0001-8494-3660
Lorenzo PiemontiDiabetes Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.ORCID http://orcid.org/0000-0002-2172-2198
Thierry BerneyCell Isolation and Transplantation Center, University of Geneva, Geneva, Switzerland.ORCID http://orcid.org/0000-0002-4230-9378
Eelco J P de KoningDepartment of Medicine, Leiden University Medical Center, Leiden, the Netherlands.
Julie Kerr-ConteEuropean Genomic Institute for Diabetes, Lille, France.
François PattouEuropean Genomic Institute for Diabetes, Lille, France.ORCID http://orcid.org/0000-0001-8388-3766
Iryna O FedkoDepartment of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
Leif GroopGenomics, Diabetes and Endocrinology, Department of Clinical Sciences, Clinical Research Centre, Lund University, Malmö, Sweden.ORCID http://orcid.org/0000-0002-0187-3263
Inga ProkopenkoSection of Genomics of Common Disease, Department of Medicine, Imperial College London, London, UK.ORCID http://orcid.org/0000-0003-1624-7457
Torben HansenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.ORCID http://orcid.org/0000-0001-8748-3831
Marc A Marti-RenomCNAG-CRG, Centre for Genomic Regulation, Barcelona Institute of Science and Technology, Barcelona, Spain.ORCID http://orcid.org/0000-0002-0151-4279
Peter FraserNuclear Dynamics Programme, The Babraham Institute, Cambridge, UK.ORCID http://orcid.org/0000-0002-0041-1227
Jorge FerrerSection of Epigenomics and Disease, Department of Medicine, and National Institute for Health Research Imperial Biomedical Research Centre, Imperial College London, London, UK. jorge.ferrer@crg.eu.ORCID http://orcid.org/0000-0002-5959-5729
National Institute for Health Research · GBUniversity of Copenhagen · DKCentre for Genomic Regulation · ESEuropean Genomic Institute for Diabetes · FRInstitució Catalana de Recerca i Estudis Avançats · ESAarhus University · DKBabraham Institute · GBBarcelona Supercomputing Center · ESBroad Institute · USCentre National de la Recherche Scientifique · FRCentro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas · ESFlorida State University · USJosep Carreras Leukaemia Research Institute · ESLeiden University Medical Center · NLLund University · SEUniversity of Geneva · CHUniversity of Surrey · GBVita-Salute San Raffaele University · ITVrije Universiteit Amsterdam · NL
Funding
European Research Council 609989European Research Council 789055Medical Research Council MR/L007150/1Medical Research Council MR/L02036X/1Wellcome Trust 101033Wellcome Trust 205915
Abstract
Genetic studies promise to provide insight into the molecular mechanisms underlying type 2 diabetes (T2D). Variants associated with T2D are often located in tissue-specific enhancer clusters or super-enhancers. So far, such domains have been defined through clustering of enhancers in linear genome maps rather than in three-dimensional (3D) space. Furthermore, their target genes are often unknown. We have created promoter capture Hi-C maps in human pancreatic islets. This linked diabetes-associated enhancers to their target genes, often located hundreds of kilobases away. It also revealed >1,300 groups of islet enhancers, super-enhancers and active promoters that form 3D hubs, some of which show coordinated glucose-dependent activity. We demonstrate that genetic variation in hubs impacts insulin secretion heritability, and show that hub annotations can be used for polygenic scores that predict T2D risk driven by islet regulatory variants. Human islet 3D chromatin architecture, therefore, provides a framework for interpretation of T2D genome-wide association study (GWAS) signals.
Indexed as
Enhancer Elements, GeneticGene Expression RegulationGene Regulatory NetworksChromatinCohort StudiesDiabetes Mellitus, Type 2Genetic Predisposition to DiseaseGenome-Wide Association StudyHumansInsulin SecretionIslets of LangerhansMolecular ConformationPromoter Regions, GeneticChromatin
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LicenceTDM
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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.