IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-017-02398-z.html
   My bibliography  Save this article

Risk of nontyphoidal Salmonella bacteraemia in African children is modified by STAT4

Author

Listed:
  • James J. Gilchrist

    (University of Oxford
    University of Oxford)

  • Anna Rautanen

    (University of Oxford)

  • Benjamin P. Fairfax

    (University of Oxford)

  • Tara C. Mills

    (University of Oxford)

  • Vivek Naranbhai

    (University of Oxford)

  • Holly Trochet

    (University of Oxford)

  • Matti Pirinen

    (University of Oxford
    Finland (FIMM) University of Helsinki)

  • Esther Muthumbi

    (KEMRI-Wellcome Trust Research Programme)

  • Salim Mwarumba

    (KEMRI-Wellcome Trust Research Programme)

  • Patricia Njuguna

    (KEMRI-Wellcome Trust Research Programme)

  • Neema Mturi

    (KEMRI-Wellcome Trust Research Programme)

  • Chisomo L. Msefula

    (College of Medicine
    College of Medicine)

  • Esther N. Gondwe

    (College of Medicine)

  • Jenny M. MacLennan

    (College of Medicine
    University of Oxford)

  • Stephen J. Chapman

    (University of Oxford
    Oxford University Hospitals)

  • Malcolm E. Molyneux

    (College of Medicine)

  • Julian C. Knight

    (University of Oxford)

  • Chris C. A. Spencer

    (University of Oxford)

  • Thomas N. Williams

    (KEMRI-Wellcome Trust Research Programme
    Imperial College)

  • Calman A. MacLennan

    (College of Medicine
    University of Oxford)

  • J. Anthony G. Scott

    (KEMRI-Wellcome Trust Research Programme
    London School of Hygiene and Tropical Medicine)

  • Adrian V. S. Hill

    (University of Oxford
    University of Oxford)

Abstract

Nontyphoidal Salmonella (NTS) is a major cause of bacteraemia in Africa. The disease typically affects HIV-infected individuals and young children, causing substantial morbidity and mortality. Here we present a genome-wide association study (180 cases, 2677 controls) and replication analysis of NTS bacteraemia in Kenyan and Malawian children. We identify a locus in STAT4, rs13390936, associated with NTS bacteraemia. rs13390936 is a context-specific expression quantitative trait locus for STAT4 RNA expression, and individuals carrying the NTS-risk genotype demonstrate decreased interferon-γ (IFNγ) production in stimulated natural killer cells, and decreased circulating IFNγ concentrations during acute NTS bacteraemia. The NTS-risk allele at rs13390936 is associated with protection against a range of autoimmune diseases. These data implicate interleukin-12-dependent IFNγ-mediated immunity as a determinant of invasive NTS disease in African children, and highlight the shared genetic architecture of infectious and autoimmune disease.

Suggested Citation

  • James J. Gilchrist & Anna Rautanen & Benjamin P. Fairfax & Tara C. Mills & Vivek Naranbhai & Holly Trochet & Matti Pirinen & Esther Muthumbi & Salim Mwarumba & Patricia Njuguna & Neema Mturi & Chisomo, 2018. "Risk of nontyphoidal Salmonella bacteraemia in African children is modified by STAT4," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02398-z
    DOI: 10.1038/s41467-017-02398-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-017-02398-z
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-017-02398-z?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
    ---><---

    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:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02398-z. 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.