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; Kenyan Bacteraemia Study Group

doi:10.1016/j.ajhg.2016.03.025

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, Kenyan Bacteraemia Study Group

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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.

Original language	English
Pages (from-to)	1092-1100
Number of pages	9
Journal	American Journal of Human Genetics
Volume	98
Issue number	6
Early online date	26 May 2016
DOIs	https://doi.org/10.1016/j.ajhg.2016.03.025
Publication status	Published - 2 Jun 2016

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2016 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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Rautanen, A., Pirinen, M., Mills, T. C., Rockett, K. A., Strange, A., Ndungu, A. W., Naranbhai, V., Gilchrist, J. J., Bellenguez, C., Freeman, C., Band, G., Bumpstead, S. J., Edkins, S., Giannoulatou, E., Gray, E., Dronov, S., Hunt, S. E., Langford, C., Pearson, R. D., ... Kenyan Bacteraemia Study Group (2016). Polymorphism in a lincRNA Associates with a Doubled Risk of Pneumococcal Bacteremia in Kenyan Children. American Journal of Human Genetics, 98(6), 1092-1100. https://doi.org/10.1016/j.ajhg.2016.03.025

@article{4428a8042f05425db7d7914d2968bfe3,

title = "Polymorphism in a lincRNA Associates with a Doubled Risk of Pneumococcal Bacteremia in Kenyan Children",

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 {\texttimes} 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.",

author = "Anna Rautanen and Matti Pirinen and Mills, \{Tara C\} and Rockett, \{Kirk A\} and Amy Strange and Ndungu, \{Anne W\} and Vivek Naranbhai and Gilchrist, \{James J\} and C{\'e}line Bellenguez and Colin Freeman and Gavin Band and Bumpstead, \{Suzannah J\} and Sarah Edkins and Eleni Giannoulatou and Emma Gray and Serge Dronov and Hunt, \{Sarah E\} and Cordelia Langford and Pearson, \{Richard D\} and Zhan Su and Damjan Vukcevic and Macharia, \{Alex W\} and Sophie Uyoga and Carolyne Ndila and Neema Mturi and Patricia Njuguna and Shebe Mohammed and Berkley, \{James A\} and Isaiah Mwangi and Salim Mwarumba and Kitsao, \{Barnes S\} and Lowe, \{Brett S\} and Morpeth, \{Susan C\} and Iqbal Khandwalla and Blackwell, \{Jenefer M\} and Elvira Bramon and Brown, \{Matthew A\} and Casas, \{Juan P\} and Aiden Corvin and Audrey Duncanson and Janusz Jankowski and Markus, \{Hugh S\} and Mathew, \{Christopher G\} and Palmer, \{Colin N A\} and Robert Plomin and Sawcer, \{Stephen J\} and Trembath, \{Richard C\} and Viswanathan, \{Ananth C\} and Wood, \{Nicholas W\} and Panos Deloukas and \{Kenyan Bacteraemia Study Group\}",

year = "2016",

month = jun,

day = "2",

doi = "10.1016/j.ajhg.2016.03.025",

language = "English",

volume = "98",

pages = "1092--1100",

journal = "American Journal of Human Genetics",

issn = "0002-9297",

publisher = "Cell Press",

number = "6",

}

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, 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 & Kenyan Bacteraemia Study Group 2016, 'Polymorphism in a lincRNA Associates with a Doubled Risk of Pneumococcal Bacteremia in Kenyan Children', American Journal of Human Genetics, vol. 98, no. 6, pp. 1092-1100. https://doi.org/10.1016/j.ajhg.2016.03.025

TY - JOUR

T1 - Polymorphism in a lincRNA Associates with a Doubled Risk of Pneumococcal Bacteremia in Kenyan Children

AU - Rautanen, Anna

AU - Pirinen, Matti

AU - Mills, Tara C

AU - Rockett, Kirk A

AU - Strange, Amy

AU - Ndungu, Anne W

AU - Naranbhai, Vivek

AU - Gilchrist, James J

AU - Bellenguez, Céline

AU - Freeman, Colin

AU - Band, Gavin

AU - Bumpstead, Suzannah J

AU - Edkins, Sarah

AU - Giannoulatou, Eleni

AU - Gray, Emma

AU - Dronov, Serge

AU - Hunt, Sarah E

AU - Langford, Cordelia

AU - Pearson, Richard D

AU - Su, Zhan

AU - Vukcevic, Damjan

AU - Macharia, Alex W

AU - Uyoga, Sophie

AU - Ndila, Carolyne

AU - Mturi, Neema

AU - Njuguna, Patricia

AU - Mohammed, Shebe

AU - Berkley, James A

AU - Mwangi, Isaiah

AU - Mwarumba, Salim

AU - Kitsao, Barnes S

AU - Lowe, Brett S

AU - Morpeth, Susan C

AU - Khandwalla, Iqbal

AU - Blackwell, Jenefer M

AU - Bramon, Elvira

AU - Brown, Matthew A

AU - Casas, Juan P

AU - Corvin, Aiden

AU - Duncanson, Audrey

AU - Jankowski, Janusz

AU - Markus, Hugh S

AU - Mathew, Christopher G

AU - Palmer, Colin N A

AU - Plomin, Robert

AU - Sawcer, Stephen J

AU - Trembath, Richard C

AU - Viswanathan, Ananth C

AU - Wood, Nicholas W

AU - Deloukas, Panos

AU - Kenyan Bacteraemia Study Group

PY - 2016/6/2

Y1 - 2016/6/2

N2 - 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.

AB - 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.

U2 - 10.1016/j.ajhg.2016.03.025

DO - 10.1016/j.ajhg.2016.03.025

M3 - Article

C2 - 27236921

SN - 0002-9297

VL - 98

SP - 1092

EP - 1100

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

IS - 6

ER -

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

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