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

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

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,MacLenna

doi

10.1038/s41467-017-02398-z

subject

Has Abstract

pub_date

2018-03-09 00:00:00

pages

1014

issue

1

issn

2041-1723

pii

10.1038/s41467-017-02398-z

journal_volume

9

pub_type

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