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

Anna Rautanen; Matti Pirinen; Tara C Mills; Kirk A Rockett; Amy Strange; Anne W Ndungu; Vivek Naranbhai; James J Gilchrist; Céline Bellenguez; Colin Freeman; Gavin Band; Suzannah J Bumpstead; Sarah Edkins; Eleni Giannoulatou; Emma Gray; Serge Dronov; Sarah E Hunt; Cordelia Langford; Richard D Pearson; Zhan Su; Damjan Vukcevic; Alex W Macharia; Sophie Uyoga; Carolyne Ndila; Neema Mturi; Patricia Njuguna; Shebe Mohammed; James A Berkley; Isaiah Mwangi; Salim Mwarumba; Barnes S Kitsao; Brett S Lowe; Susan C Morpeth; Iqbal Khandwalla; Jenefer M Blackwell; Elvira Bramon; Matthew A Brown; Juan P Casas; Aiden Corvin; Audrey Duncanson; Janusz Jankowski; Hugh S Markus; Christopher G Mathew; Colin N A Palmer; Robert Plomin; Stephen J Sawcer; Richard C Trembath; Ananth C Viswanathan; Nicholas W Wood; Panos Deloukas; Leena Peltonen; Thomas N Williams; J Anthony G Scott; Stephen J Chapman; Peter Donnelly; Adrian V S Hill; Chris C A Spencer; Kilifi Bacteraemia Surveillance Group

doi:10.1016/j.ajhg.2016.03.025

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

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

Anna Rautanen, Matti Pirinen, Tara C Mills, Kirk A Rockett, Amy Strange, Anne W Ndungu, Vivek Naranbhai, James J Gilchrist, Céline Bellenguez, Colin Freeman, …

American journal of human genetics, Vol.98(6), pp.1092-1100

02/06/2016

DOI: https://doi.org/10.1016/j.ajhg.2016.03.025

PMID: 27236921

Abstract

Adolescent

Bacteremia - genetics

Bacteremia - microbiology

Bacteremia - pathology

Case-Control Studies

Child

Child, Preschool

Genome-Wide Association Study

Humans

Infant

Infant, Newborn

Kenya - epidemiology

Pneumonia, Pneumococcal - genetics

Pneumonia, Pneumococcal - microbiology

Pneumonia, Pneumococcal - pathology

Polymorphism, Genetic - genetics

Risk Factors

RNA, Long Noncoding - genetics

Streptococcus pneumoniae - genetics

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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Title: Polymorphism in a lincRNA Associates with a Doubled Risk of Pneumococcal Bacteremia in Kenyan Children
Creators - without role: Anna Rautanen - Wellcome Centre for Human Genetics
Matti Pirinen - Wellcome Centre for Human Genetics
Tara C Mills - Wellcome Centre for Human Genetics
Kirk A Rockett - Wellcome Centre for Human Genetics
Amy Strange - Wellcome Centre for Human Genetics
Anne W Ndungu - University of Oxford
Vivek Naranbhai - Wellcome Centre for Human Genetics
James J Gilchrist
Céline Bellenguez - Wellcome Centre for Human Genetics
Colin Freeman - Wellcome Centre for Human Genetics
Gavin Band - Wellcome Centre for Human Genetics
Suzannah J Bumpstead - Wellcome Sanger Institute
Sarah Edkins - Wellcome Sanger Institute
Eleni Giannoulatou - University of Oxford
Emma Gray - Wellcome Sanger Institute
Serge Dronov - Wellcome Sanger Institute
Sarah E Hunt - Wellcome Sanger Institute
Cordelia Langford - Wellcome Sanger Institute
Richard D Pearson - University of Oxford
Zhan Su - Wellcome Centre for Human Genetics
Damjan Vukcevic - University of Oxford
Alex W Macharia - Kenya Medical Research Institute
Sophie Uyoga - Kenya Medical Research Institute
Carolyne Ndila - Kenya Medical Research Institute
Neema Mturi - Kenya Medical Research Institute
Patricia Njuguna - Kenya Medical Research Institute
Shebe Mohammed - Kenya Medical Research Institute
James A Berkley - Kenya Medical Research Institute
Isaiah Mwangi - Kenya Medical Research Institute
Salim Mwarumba - Kenya Medical Research Institute
Barnes S Kitsao - Kenya Medical Research Institute
Brett S Lowe - Kenya Medical Research Institute
Susan C Morpeth - Kenya Medical Research Institute
Iqbal Khandwalla - Kenya Medical Research Institute
Jenefer M Blackwell - University of Western Australia
Elvira Bramon - South London and Maudsley NHS Foundation Trust
Matthew A Brown - Princess Alexandra Hospital
Juan P Casas - Farr Institute
Aiden Corvin - Trinity College Dublin
Audrey Duncanson - Wellcome Trust
Janusz Jankowski - Peninsula College of Medicine and Dentistry
Hugh S Markus - University of Cambridge
Christopher G Mathew - King's College London
Colin N A Palmer - University of Dundee
Robert Plomin - King's College London
Stephen J Sawcer - Addenbrooke's Hospital
Richard C Trembath - Queen Mary University of London
Ananth C Viswanathan - Moorfields Eye Hospital NHS Foundation Trust
Nicholas W Wood - National Hospital for Neurology and Neurosurgery
Panos Deloukas - Wellcome Sanger Institute
Leena Peltonen - Wellcome Sanger Institute
Thomas N Williams - Kenya Medical Research Institute
J Anthony G Scott
Stephen J Chapman
Peter Donnelly - University of Oxford
Adrian V S Hill - University of Oxford
Chris C A Spencer - Wellcome Centre for Human Genetics
Kilifi Bacteraemia Surveillance Group
Publication Details: American journal of human genetics, Vol.98(6), pp.1092-1100
Grant note: PDA/02/06/016 / Department of Health G1001712 / Medical Research Council G0901310 / Medical Research Council MR/M007367/1 / Medical Research Council 294557 / European Research Council
Identifiers: 9938316308331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article