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

Journal: American journal of human genetics

Volume: 98

Issue: 6

Year of Publication: 2017

Affiliated Institutions:  Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX BN, UK. Electronic address: anna.rautanen@well.ox.ac.uk. Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX BN, UK. Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX BN, UK; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB SA, UK. Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX BN, UK; Department of Paediatrics, University of Oxford, Oxford OX DU, UK. Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB SA, UK. KEMRI-Wellcome Trust Research Programme, Kilifi , Kenya. KEMRI-Wellcome Trust Research Programme, Kilifi , Kenya; Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX DU, UK; Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London WCE HT, UK. Cambridge Institute for Medical Research and Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB QP, UK; Telethon Kids Institute, The University of Western Australia, Subiaco, WA , Australia. National Institute for Health Research (NIHR) Biomedical Research Centre for Mental Health at the South London and Maudsley National Health Service (NHS) Foundation Trust and Institute of Psychiatry, King's College London, Denmark Hill, London SE AF, UK. Institute of Health and Biomedical Innovation, Queensland University of Technology, Translational Research Institute, Princess Alexandra Hospital, Brisbane, QLD , Australia. Farr Institute of Health Informatics, University College London, London NW DA, UK. Neuropsychiatric Genetics Research Group, Institute of Molecular Medicine, Trinity College Dublin, Dublin , Ireland. Molecular and Physiological Sciences, The Wellcome Trust, London NW BE, UK. Associate Deans Office, John Bull Building, Peninsula School of Medicine and Dentistry, Plymouth PL BU, UK. Department of Neurology, University of Cambridge, Cambridge CB QQ, UK. Division of Genetics and Molecular Medicine, King's College London, London SE RT, UK; Sydney Brenner Institute for Molecular Bioscience, University of Witwatersrand, Johannesburg , South Africa. Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee DD SY, UK. MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, De Crespigny Park, London SE AF, UK. Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB QQ, UK. London School of Medicine and Dentistry, Queen Mary University of London, London E AT, UK. NIHR Biomedical Research Centre at Moorfields Eye Hospital NHSFT and UCL Institute of Ophthalmology, London ECV PD, UK. Department of Molecular Neuroscience, Institute of Neurology, Queen Square, London WCN BG, UK. KEMRI-Wellcome Trust Research Programme, Kilifi , Kenya; Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX DU, UK; Department of Medicine, Imperial College, London WNY, UK; INDEPTH Network, Accra, Ghana. Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX BN, UK; Oxford Centre for Respiratory Medicine, Churchill Hospital Site, Oxford University Hospitals, Oxford OX LE, UK. Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX BN, UK; Department of Statistics, University of Oxford, Oxford OX TG, UK. Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX BN, UK; The Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX DQ, UK.

Abstract summary 

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.

Authors & Co-authors:  Rautanen Pirinen Mills Rockett Strange Ndungu Naranbhai Gilchrist Bellenguez Freeman Band Bumpstead Edkins Giannoulatou Gray Dronov Hunt Langford Pearson Su Vukcevic Macharia Uyoga Ndila Mturi Njuguna Mohammed Berkley Mwangi Mwarumba Kitsao Lowe Morpeth Khandwalla Blackwell Bramon Brown Casas Corvin Duncanson Jankowski Markus Mathew Palmer Plomin Sawcer Trembath Viswanathan Wood Deloukas Peltonen Williams Scott Chapman Donnelly Hill Spencer

Study Outcome 

Source Link: Visit source

Statistics
Citations :  Lillie P.J., Allen J., Hall C., Walsh C., Adams K., Thaker H., Moss P., Barlow G.D. Long-term mortality following bloodstream infection. Clin. Microbiol. Infect. 2013;19:955–960.
Authors :  60
Identifiers
Doi : 10.1016/j.ajhg.2016.03.025
SSN : 1537-6605
Study Population
Male,Female
Mesh Terms
Adolescent
Other Terms
Study Design
Study Approach
Country of Study
Kenya
Publication Country
United States