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

Rautanen, Anna, Pirinen, Matti, Mills, Tara C., Rockett, Kirk A., Strange, Amy, Ndungu, Anne W., Naranbhai, Vivek, Gilchrist, James J., Bellenguez, Celine, Freeman, Colin, Band, Gavin, Bumpstead, Suzannah J., Edkins, Sarah, Giannoulatou, Eleni, Gray, Emma, Dronov, Serge, Hunt, Sarah E., Langford, Cordelia, Pearson, Richard D., Su, Zhan, Vukcevic, Damjan, Macharia, Alex W., Uyoga, Sophie, Ndila, Carolyne, Mturi, Neema, Njuguna, Patricia, Mohammed, Shebe, Berkley, James A., Mwangi, Isaiah, Mwarumba, Salim, Kitsao, Barnes S., Lowe, Brett S., Morpeth, Susan C., Khandwalla, Iqbal, Blackwell, Jenefer M., Bramon, Elvira, Brown, Matthew A., Casas, Juan P., Corvin, Aiden, Duncanson, Audrey, Jankowski, Janusz, Markus, Hugh S., Mathew, Christopher G., Palmer, Colin N. A., Plomin, Robert, Sawcer, Stephen J., Trembath, Richard C., Viswanathan, Ananth C., Wood, Nicholas W., Deloukas, Panos, Peltonen, Leena, Williams, Thomas N., Scott, J. Anthony G., Chapman, Stephen J., Donnelly, Peter, Hill, Adrian V. S. and Spencer, Chris C. A. (2016) Polymorphism in a lincRNA Associates with a Doubled Risk of Pneumococcal Bacteremia in Kenyan Children. American Journal of Human Genetics, 98 6: 1092-1100. doi:10.1016/j.ajhg.2016.03.025

Author Rautanen, Anna
Pirinen, Matti
Mills, Tara C.
Rockett, Kirk A.
Strange, Amy
Ndungu, Anne W.
Naranbhai, Vivek
Gilchrist, James J.
Bellenguez, Celine
Freeman, Colin
Band, Gavin
Bumpstead, Suzannah J.
Edkins, Sarah
Giannoulatou, Eleni
Gray, Emma
Dronov, Serge
Hunt, Sarah E.
Langford, Cordelia
Pearson, Richard D.
Su, Zhan
Vukcevic, Damjan
Macharia, Alex W.
Uyoga, Sophie
Ndila, Carolyne
Mturi, Neema
Njuguna, Patricia
Mohammed, Shebe
Berkley, James A.
Mwangi, Isaiah
Mwarumba, Salim
Kitsao, Barnes S.
Lowe, Brett S.
Morpeth, Susan C.
Khandwalla, Iqbal
Blackwell, Jenefer M.
Bramon, Elvira
Brown, Matthew A.
Casas, Juan P.
Corvin, Aiden
Duncanson, Audrey
Jankowski, Janusz
Markus, Hugh S.
Mathew, Christopher G.
Palmer, Colin N. A.
Plomin, Robert
Sawcer, Stephen J.
Trembath, Richard C.
Viswanathan, Ananth C.
Wood, Nicholas W.
Deloukas, Panos
Peltonen, Leena
Williams, Thomas N.
Scott, J. Anthony G.
Chapman, Stephen J.
Donnelly, Peter
Hill, Adrian V. S.
Spencer, Chris C. A.
Title Polymorphism in a lincRNA Associates with a Doubled Risk of Pneumococcal Bacteremia in Kenyan Children
Journal name American Journal of Human Genetics   Check publisher's open access policy
ISSN 1537-6605
Publication date 2016-06-02
Year available 2016
Sub-type Article (original research)
DOI 10.1016/j.ajhg.2016.03.025
Open Access Status Not Open Access
Volume 98
Issue 6
Start page 1092
End page 1100
Total pages 9
Place of publication Cambridge, United States
Publisher Cell Press
Language eng
Formatted 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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
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