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GWAS Study

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

Rautanen A, Pirinen M, Mills TC et al.

27236921 PubMed ID
GWAS Study Type
4555 Participants
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Chapter I

Publication Details

Comprehensive information about this research publication

Authors

RA
Rautanen A
PM
Pirinen M
MT
Mills TC
RK
Rockett KA
SA
Strange A
NA
Ndungu AW
NV
Naranbhai V
GJ
Gilchrist JJ
BC
Bellenguez C
FC
Freeman C
BG
Band G
BS
Bumpstead SJ
ES
Edkins S
GE
Giannoulatou E
GE
Gray E
DS
Dronov S
HS
Hunt SE
LC
Langford C
PR
Pearson RD
SZ
Su Z
VD
Vukcevic D
MA
Macharia AW
US
Uyoga S
NC
Ndila C
MN
Mturi N
NP
Njuguna P
MS
Mohammed S
BJ
Berkley JA
MI
Mwangi I
MS
Mwarumba S
KB
Kitsao BS
LB
Lowe BS
MS
Morpeth SC
KI
Khandwalla I
BJ
Blackwell JM
BE
Bramon E
BM
Brown MA
CJ
Casas JP
CA
Corvin A
DA
Duncanson A
JJ
Jankowski J
MH
Markus HS
MC
Mathew CG
PC
Palmer CNA
PR
Plomin R
SS
Sawcer SJ
TR
Trembath RC
VA
Viswanathan AC
WN
Wood NW
DP
Deloukas P
PL
Peltonen L
WT
Williams TN
SJ
Scott JAG
CS
Chapman SJ
DP
Donnelly P
HA
Hill AVS
SC
Spencer CCA
Chapter II

Abstract

Summary of the research findings

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.

429 African ancestry cases, 2,677 African ancestry controls

Chapter III

Study Statistics

Key metrics and study information

4555
Total Participants
GWAS
Study Type
Yes
Replicated
113 African ancestry cases, 1,336 African ancestry controls
Replication Participants
African unspecified
Ancestry
Kenya
Recruitment Country
Chapter IV

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