Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Human pancreatic islet three-dimensional chromatin architecture provides insights into the genetics of type 2 diabetes

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Disruption of chromatin folding domains by somatic genomic rearrangements in human cancer

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  5. Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  • Irene Miguel-Escalada
  • Silvia Bonàs-Guarch
  • Inês Cebola
  • Joan Ponsa-Cobas
  • Julen Mendieta-Esteban
  • Goutham Atla
  • Biola M Javierre
  • Delphine M Y Rolando
  • Irene Farabella
  • Claire C Morgan
  • Javier García-Hurtado
  • Anthony Beucher
  • Ignasi Morán
  • Lorenzo Pasquali
  • Mireia Ramos-Rodríguez
  • Emil V R Appel
  • Allan Linneberg
  • Anette P Gjesing
  • Daniel R Witte
  • Oluf Pedersen
  • Niels Grarup
  • Philippe Ravassard
  • David Torrents
  • Josep M Mercader
  • Lorenzo Piemonti
  • Thierry Berney
  • Eelco J P de Koning
  • Julie Kerr-Conte
  • François Pattou
  • Iryna O Fedko
  • Leif Groop
  • Inga Prokopenko
  • Torben Hansen
  • Marc A Marti-Renom
  • Peter Fraser
  • Jorge Ferrer
Vis graf over relationer

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.

OriginalsprogEngelsk
TidsskriftNature Genetics
Vol/bind51
Udgave nummer7
Sider (fra-til)1137-1148
Antal sider12
ISSN1061-4036
DOI
StatusUdgivet - jul. 2019

ID: 57516974