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- Title
Risk of nontyphoidal Salmonella bacteraemia in African children is modified by STAT4.
- Authors
Gilchrist, James J.; Rautanen, Anna; Fairfax, Benjamin P.; Mills, Tara C.; Naranbhai, Vivek; Trochet, Holly; Pirinen, Matti; Muthumbi, Esther; Mwarumba, Salim; Njuguna, Patricia; Mturi, Neema; Msefula, Chisomo L.; Gondwe, Esther N.; MacLennan, Jenny M.; Chapman, Stephen J.; Molyneux, Malcolm E.; Knight, Julian C.; Spencer, Chris C. A.; Williams, Thomas N.; MacLennan, Calman A.
- 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 contextspecific 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.
- Subjects
NATIONAL Trust for Scotland; LOCUS (Genetics); BACTEREMIA; KILLER cells; SALMONELLA; JUVENILE diseases; INTERFERON receptors; AUTOIMMUNE diseases
- Publication
Nature Communications, 2018, Vol 9, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-017-02398-z