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

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 SuDamjan 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, Kenyan Bacteraemia Study Group

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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.

    Original languageEnglish
    Pages (from-to)1092-1100
    Number of pages9
    JournalAmerican Journal of Human Genetics
    Volume98
    Issue number6
    Early online date26 May 2016
    DOIs
    Publication statusPublished - 2 Jun 2016

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