Polymorphism in a lincRNA Associates with a Doubled Risk of Pneumococcal Bacteremia in Kenyan Children
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Published version
Author(s)
Type
Journal Article
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.
Date Issued
2016-05-26
Date Acceptance
2016-03-28
Citation
The American Journal of Human Genetics, 2016, 98 (6), pp.1092-1100
ISSN
0002-9297
Publisher
Elsevier
Start Page
1092
End Page
1100
Journal / Book Title
The American Journal of Human Genetics
Volume
98
Issue
6
Copyright Statement
© 2016 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
License URL
Sponsor
Commission of the European Communities
Wellcome Trust
Grant Number
242095
091758/B/10/Z
Subjects
Genetics & Heredity
06 Biological Sciences
11 Medical And Health Sciences
Publication Status
Published