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Human pancreatic is...
Human pancreatic islet three-dimensional chromatin architecture provides insights into the genetics of type 2 diabetes
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- Miguel-Escalada, Irene (author)
- Imperial College London
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- Bonàs-Guarch, Silvia (author)
- Imperial College London
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- Cebola, Inês (author)
- Imperial College London
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- Ponsa-Cobas, Joan (author)
- Imperial College London
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- Mendieta-Esteban, Julen (author)
- Center for Genomic Regulation (CRG)
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- Atla, Goutham (author)
- Center for Genomic Regulation (CRG),Imperial College London
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- Javierre, Biola M. (author)
- University of Cambridge
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- Rolando, Delphine M.Y. (author)
- Imperial College London
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- Farabella, Irene (author)
- Center for Genomic Regulation (CRG)
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- Morgan, Claire C. (author)
- Imperial College London,Center for Genomic Regulation (CRG)
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- García-Hurtado, Javier (author)
- Center for Genomic Regulation (CRG)
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- Beucher, Anthony (author)
- Imperial College London
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- Morán, Ignasi (author)
- Imperial College London,Center for Genomic Regulation (CRG)
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- Pasquali, Lorenzo (author)
- Hospital Universitari Germans Trias i Pujol
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- Ramos-Rodríguez, Mireia (author)
- Hospital Universitari Germans Trias i Pujol
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- Appel, Emil V.R. (author)
- University of Copenhagen
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- Linneberg, Allan (author)
- Frederiksberg Hospital,University of Copenhagen
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- Gjesing, Anette P. (author)
- University of Copenhagen
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- Witte, Daniel R. (author)
- Danish Diabetes Academy,Aarhus University
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- Pedersen, Oluf (author)
- University of Copenhagen
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- Grarup, Niels (author)
- University of Copenhagen
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- Ravassard, Philippe (author)
- Paris-Sorbonne University
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- Torrents, David (author)
- Catalan Institution for Research and Advanced Studies,Center for Genomic Regulation (CRG)
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- Mercader, Josep M. (author)
- Center for Genomic Regulation (CRG),Massachusetts General Hospital,Broad Institute
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- Piemonti, Lorenzo (author)
- Vita-Salute San Raffaele University,San Raffaele Scientific Institute
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- Berney, Thierry (author)
- University of Geneva
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- de Koning, Eelco J.P. (author)
- Leiden University Medical Centre,Hubrecht Institute
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- Kerr-Conte, Julie (author)
- European Genome Institute for Diabetes (EGID) UMR 8199
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- Pattou, François (author)
- European Genome Institute for Diabetes (EGID) UMR 8199
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- Fedko, Iryna O. (author)
- Vrije Universiteit Amsterdam
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- Groop, Leif (author)
- Lund University,Lunds universitet,Translationell muskelforskning,Forskargrupper vid Lunds universitet,LUBIN Lab- Lunds laboratorium för neurokirurgisk hjärnskadeforskning,Translational Muscle Research,Lund University Research Groups,LUBIN Lab- Lund Brain Injury laboratory for Neurosurgical research
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- Prokopenko, Inga (author)
- University of Surrey,Imperial College London
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- Hansen, Torben (author)
- University of Copenhagen
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- Marti-Renom, Marc A. (author)
- Pompeu Fabra University,Center for Genomic Regulation (CRG),Catalan Institution for Research and Advanced Studies
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- Fraser, Peter (author)
- Florida State University
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- Ferrer, Jorge (author)
- Imperial College London,Center for Genomic Regulation (CRG)
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(creator_code:org_t)
- 2019-06-28
- 2019
- English.
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:7, s. 1137-1148
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http://dx.doi.org/10...
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Abstract
Subject headings
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- 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.
Subject headings
- NATURVETENSKAP -- Biologi -- Genetik (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Genetics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Miguel-Escalada, ...
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Bonàs-Guarch, Si ...
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Cebola, Inês
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Ponsa-Cobas, Joa ...
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Mendieta-Esteban ...
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Atla, Goutham
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show more...
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Javierre, Biola ...
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Rolando, Delphin ...
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Farabella, Irene
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Morgan, Claire C ...
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García-Hurtado, ...
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Beucher, Anthony
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Morán, Ignasi
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Pasquali, Lorenz ...
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Ramos-Rodríguez, ...
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Appel, Emil V.R.
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Linneberg, Allan
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Gjesing, Anette ...
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Witte, Daniel R.
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Pedersen, Oluf
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Grarup, Niels
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Ravassard, Phili ...
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Torrents, David
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Mercader, Josep ...
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Piemonti, Lorenz ...
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Berney, Thierry
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de Koning, Eelco ...
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Kerr-Conte, Juli ...
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Pattou, François
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Fedko, Iryna O.
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Groop, Leif
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Prokopenko, Inga
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Hansen, Torben
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Marti-Renom, Mar ...
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Fraser, Peter
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Ferrer, Jorge
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Genetics
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
- Articles in the publication
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Nature Genetics
- By the university
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Lund University