Polymorphism in a lincRNA Associates with a Doubled Risk of Pneumococcal Bacteremia in Kenyan Children.


Kenyan Bacteraemia Study Group; Wellcome Trust Case Control Consortium 2 (WTCCC2); Rautanen, A; Pirinen, M; Mills, TC; Rockett, KA; Strange, A; Ndungu, AW; Naranbhai, V; Gilchrist, JJ; Bellenguez, C; Freeman, C; Band, G; Bumpstead, SJ; Edkins, S; Giannoulatou, E; Gray, E; Dronov, S; Hunt, SE; Langford, C; Pearson, RD; Su, Z; Vukcevic, D; Macharia, AW; Uyoga, S; Ndila, C; Mturi, N; Njuguna, P; Mohammed, S; Berkley, JA; Mwangi, I; Mwarumba, S; Kitsao, BS; Lowe, BS; Morpeth, SC; Khandwalla, I; Kilifi Bacteraemia Surveillance Group; Blackwell, JM; Bramon, E; Brown, MA; Casas, JP; Corvin, A; Duncanson, A; Jankowski, J; Markus, HS; Mathew, CG; Palmer, CN; Plomin, R; Sawcer, SJ; Trembath, RC; Viswanathan, AC; Wood, NW; Deloukas, P; Peltonen, L; Williams, TN; Scott, JA; Chapman, SJ; Donnelly, P; Hill, AV; Spencer, CC; (2016) Polymorphism in a lincRNA Associates with a Doubled Risk of Pneumococcal Bacteremia in Kenyan Children. American journal of human genetics, 98 (6). pp. 1092-100. ISSN 0002-9297 DOI: 10.1016/j.ajhg.2016.03.025

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Abstract

: Bacteremia (bacterial bloodstream infection) is a major cause of illness and death in sub-Saharan Africa but little is known about the role of human genetics in susceptibility. We conducted a genome-wide association study of bacteremia susceptibility in more than 5,000 Kenyan children as part of the Wellcome Trust Case Control Consortium 2 (WTCCC2). Both the blood-culture-proven bacteremia case subjects and healthy infants as controls were recruited from Kilifi, on the east coast of Kenya. Streptococcus pneumoniae is the most common cause of bacteremia in Kilifi and was thus the focus of this study. We identified an association between polymorphisms in a long intergenic non-coding RNA (lincRNA) gene (AC011288.2) and pneumococcal bacteremia and replicated the results in the same population (p combined = 1.69 × 10(-9); OR = 2.47, 95% CI = 1.84-3.31). The susceptibility allele is African specific, derived rather than ancestral, and occurs at low frequency (2.7% in control subjects and 6.4% in case subjects). Our further studies showed AC011288.2 expression only in neutrophils, a cell type that is known to play a major role in pneumococcal clearance. Identification of this novel association will further focus research on the role of lincRNAs in human infectious disease.<br/>

Item Type: Article
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
PubMed ID: 27236921
Web of Science ID: 377286000005
URI: http://researchonline.lshtm.ac.uk/id/eprint/2551581

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