Repository logo
 

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

Published version
Peer-reviewed

Type

Article

Change log

Authors

Kenyan Bacteraemia Study Group 
Wellcome Trust Case Control Consortium 2 (WTCCC2) 
Rautanen, Anna 
Pirinen, Matti 
Mills, Tara C 

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.

Description

Keywords

Adolescent, Bacteremia, Case-Control Studies, Child, Child, Preschool, Genome-Wide Association Study, Humans, Infant, Infant, Newborn, Kenya, Pneumonia, Pneumococcal, Polymorphism, Genetic, RNA, Long Noncoding, Risk Factors, Streptococcus pneumoniae

Journal Title

Am J Hum Genet

Conference Name

Journal ISSN

0002-9297
1537-6605

Volume Title

98

Publisher

Elsevier BV
Sponsorship
Wellcome Trust (090770/Z/09/Z)
Wellcome Trust (Grant ID: 084716/Z/08/Z)