Kenyan Bacteraemia Study Group
Wellcome Trust Case Control Consortium
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
Kilifi Bacteraemia Surveillance Group
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
Am J Hum Genet. 2016;981092-1100
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 x 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.
