| dc.contributor.author |
Gilchrist JJ, Rautanen A, Fairfax BP, Mills TC, Naranbhai V, Trochet H, Pirinen M, Muthumbi E, Mwarumba S, Njuguna P, Mturi N, Msefula CL, Gondwe EN, MacLennan JM, Chapman SJ, Molyneux ME, Knight JC, Spencer CCA, Williams TN, MacLennan CA, Scott JAG, Hill AVS. |
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| dc.description.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. |
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