Title :

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.

Authors :

Gilchrist, J.J., Rautanen, A., Fairfax, B.P., Mills, T.C., Naranbhai, V., Trochet, H., Pirinen, M., Muthumbi, E., Mwarumba, S., Njuguna, P., Mturi, N., Msefula, C.L., Gondwe, E.N., MacLennan, J.M., Chapman, S.J., Molyneux, M.E., Knight, J.C., Spencer, C.C.A., Williams, T.N., MacLennan, C.A., Scott, J.A.G., Hill, A.V.S.

PubMed link :

Journals :

Nature Communications. 2018