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

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Anna Rautanen, Matti Pirinen, Tara C. Mills, Kirk A. Rockett, Amy Strange, Anne W. Ndungu, Vivek Naranbhai, James J. Gilchrist, Céline Bellenguez, Colin Freeman, Gavin Band, Suzannah J. Bumpstead, Sarah Edkins, Eleni Giannoulatou, Emma Gray, Serge Dronov, Sarah E. Hunt, Cordelia Langford, Richard D. Pearson, Zhan Su & 37 more Damjan Vukcevic, Alex W. Macharia, Sophie Uyoga, Carolyne Ndila, Neema Mturi, Patricia Njuguna, Shebe Mohammed, James A. Berkley, Isaiah Mwangi, Salim Mwarumba, Barnes S. Kitsao, Brett S. Lowe, Susan C. Morpeth, Iqbal Khandwalla, Jenefer M. Blackwell, Elvira Bramon, Matthew A. Brown, Juan P. Casas, Aiden Corvin, Audrey Duncanson, Janusz Jankowski, Hugh S. Markus, Christopher G. Mathew, Colin N.A. Palmer, Robert Plomin, Stephen J. Sawcer, Richard C. Trembath, Ananth C. Viswanathan, Nicholas W. Wood, Panos Deloukas, Leena Peltonen, Thomas N. Williams, J. Anthony G. Scott, Stephen J. Chapman, Peter Donnelly, Adrian V.S. Hill, Chris C.A. Spencer

Original languageEnglish
Pages (from-to)1092 - 1100
JournalAmerican Journal of Human Genetics
Volume98
Issue number6
Early online date26 May 2016
DOIs
Accepted/In press28 Mar 2016
E-pub ahead of print26 May 2016
Published2 Jun 2016

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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.

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