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Publication Detail
Polymorphism in a lincRNA Associates with a Doubled Risk of Pneumococcal Bacteremia in Kenyan Children
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Article
  • Authors:
    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, Blackwell JM, Bramon E, Brown MA, Casas JP, Corvin A, Duncanson A, Jankowski J, Markus HS, Mathew CG, Palmer CNA, Plomin R, Sawcer SJ, Trembath RC, Viswanathan AC, Wood NW, Deloukas P, Peltonen L, Williams TN, Scott JAG, Chapman SJ, Donnelly P, Hill AVS, Spencer CCA
  • Publication date:
    26/05/2016
  • Pagination:
    1092, 1100
  • Journal:
    American Journal of Human Genetics
  • Volume:
    98
  • Issue:
    6
  • Status:
    Published
  • Print ISSN:
    0002-9297
Abstract
© 2016 The Authors.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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