IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v467y2010i7314d10.1038_nature09386.html
   My bibliography  Save this article

A trans-acting locus regulates an anti-viral expression network and type 1 diabetes risk

Author

Listed:
  • Matthias Heinig

    (Max-Delbrück-Center for Molecular Medicine (MDC), Robert-Rössle-Straße 10
    Max Planck Institute for Molecular Genetics, Ihnestraße 63-73, 14195 Berlin, Germany)

  • Enrico Petretto

    (Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK
    Faculty of Medicine, Imperial College London, Praed Street, London W2 1PG, UK)

  • Chris Wallace

    (Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 OXY, UK)

  • Leonardo Bottolo

    (Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK
    Faculty of Medicine, Imperial College London, Praed Street, London W2 1PG, UK)

  • Maxime Rotival

    (INSERM UMRS 937, Pierre and Marie Curie University (UPMC, Paris 6) and Medical School, 91 Boulevard de l’Hôpital, Paris 75013, France)

  • Han Lu

    (Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK)

  • Yoyo Li

    (Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK)

  • Rizwan Sarwar

    (Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK)

  • Sarah R. Langley

    (Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK)

  • Anja Bauerfeind

    (Max-Delbrück-Center for Molecular Medicine (MDC), Robert-Rössle-Straße 10)

  • Oliver Hummel

    (Max-Delbrück-Center for Molecular Medicine (MDC), Robert-Rössle-Straße 10)

  • Young-Ae Lee

    (Max-Delbrück-Center for Molecular Medicine (MDC), Robert-Rössle-Straße 10
    Pediatric Pneumology and Immunology, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany)

  • Svetlana Paskas

    (Max-Delbrück-Center for Molecular Medicine (MDC), Robert-Rössle-Straße 10)

  • Carola Rintisch

    (Max-Delbrück-Center for Molecular Medicine (MDC), Robert-Rössle-Straße 10)

  • Kathrin Saar

    (Max-Delbrück-Center for Molecular Medicine (MDC), Robert-Rössle-Straße 10)

  • Jason Cooper

    (Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 OXY, UK)

  • Rachel Buchan

    (Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK)

  • Elizabeth E. Gray

    (University of California San Francisco)

  • Jason G. Cyster

    (University of California San Francisco)

  • Jeanette Erdmann

    (Universität zu Lübeck, Medizinische Klinik II, 23538 Lübeck, Germany)

  • Christian Hengstenberg

    (Klinik und Poliklinik für Innere Medizin II, Universität Regensburg)

  • Seraya Maouche

    (INSERM UMRS 937, Pierre and Marie Curie University (UPMC, Paris 6) and Medical School, 91 Boulevard de l’Hôpital, Paris 75013, France)

  • Willem H. Ouwehand

    (University of Cambridge and National Health Service Blood and Transplant, Cambridge CB2 0PT, UK
    Human Genetics, Wellcome Trust Sanger Institute, Genome Campus)

  • Catherine M. Rice

    (Human Genetics, Wellcome Trust Sanger Institute, Genome Campus)

  • Nilesh J. Samani

    (University of Leicester and Leicester NIHR Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester LE3 9QP, UK)

  • Heribert Schunkert

    (Universität zu Lübeck, Medizinische Klinik II, 23538 Lübeck, Germany)

  • Alison H. Goodall

    (University of Leicester and Leicester NIHR Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester LE3 9QP, UK)

  • Herbert Schulz

    (Max-Delbrück-Center for Molecular Medicine (MDC), Robert-Rössle-Straße 10)

  • Helge G. Roider

    (Max Planck Institute for Molecular Genetics, Ihnestraße 63-73, 14195 Berlin, Germany)

  • Martin Vingron

    (Max Planck Institute for Molecular Genetics, Ihnestraße 63-73, 14195 Berlin, Germany)

  • Stefan Blankenberg

    (Medizinische Klinik und Poliklinik, Johannes-Gutenberg Universität Mainz, Universitätsmedizin, Langenbeckstrasse 1, 55131 Mainz, Germany)

  • Thomas Münzel

    (Medizinische Klinik und Poliklinik, Johannes-Gutenberg Universität Mainz, Universitätsmedizin, Langenbeckstrasse 1, 55131 Mainz, Germany)

  • Tanja Zeller

    (Medizinische Klinik und Poliklinik, Johannes-Gutenberg Universität Mainz, Universitätsmedizin, Langenbeckstrasse 1, 55131 Mainz, Germany)

  • Silke Szymczak

    (Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Maria-Goeppert-Straße 1, 23562 Lübeck, Germany)

  • Andreas Ziegler

    (Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Maria-Goeppert-Straße 1, 23562 Lübeck, Germany)

  • Laurence Tiret

    (INSERM UMRS 937, Pierre and Marie Curie University (UPMC, Paris 6) and Medical School, 91 Boulevard de l’Hôpital, Paris 75013, France)

  • Deborah J. Smyth

    (Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 OXY, UK)

  • Michal Pravenec

    (Institute of Physiology, Czech Academy of Sciences and Centre for Applied Genomics, Videnska 1083, 14220 Prague 4, Czech Republic)

  • Timothy J. Aitman

    (Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK)

  • Francois Cambien

    (INSERM UMRS 937, Pierre and Marie Curie University (UPMC, Paris 6) and Medical School, 91 Boulevard de l’Hôpital, Paris 75013, France)

  • David Clayton

    (Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 OXY, UK)

  • John A. Todd

    (Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 OXY, UK)

  • Norbert Hubner

    (Max-Delbrück-Center for Molecular Medicine (MDC), Robert-Rössle-Straße 10
    CC4, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany)

  • Stuart A. Cook

    (Medical Research Council Clinical Sciences Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK
    National Heart and Lung Institute, Imperial College, Dovehouse Street, London SW3 6LY, UK)

Abstract

Gene networks linked to type 1 diabetes Genome-wide association studies (GWAS) have highlighted a number of genes with connections to type 1 diabetes and other common diseases, but in most instances the mechanism by which DNA variation affects disease risk is far from clear. Recent advances in rat genomics now make a systems-genetics approach possible, which should help to reveal links between diseases and gene functions. Using gene expression studies across seven types of rat tissue, together with GWAS and human genetics, Heinig et al. have now identified the inflammatory network driven by interferon regulatory factor 7 (IRF7) as a contributor to type 1 diabetes risk. They also implicate the innate viral response pathway and macrophages in the aetiology of the disease. The study shows how co-expression networks across species provide functional annotation of genes, and how this can be used to reveal a signal of common genetic variation of small effect that is not detected by GWAS.

Suggested Citation

  • Matthias Heinig & Enrico Petretto & Chris Wallace & Leonardo Bottolo & Maxime Rotival & Han Lu & Yoyo Li & Rizwan Sarwar & Sarah R. Langley & Anja Bauerfeind & Oliver Hummel & Young-Ae Lee & Svetlana , 2010. "A trans-acting locus regulates an anti-viral expression network and type 1 diabetes risk," Nature, Nature, vol. 467(7314), pages 460-464, September.
    • Handle: RePEc:nat:nature:v:467:y:2010:i:7314:d:10.1038_nature09386
    DOI: 10.1038/nature09386
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature09386
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/nature09386?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:467:y:2010:i:7314:d:10.1038_nature09386. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.