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

A. Rautanen; M. Pirinen; T.C. Mills; K.A. Rockett; A. Strange; A.W. Ndungu; V. Naranbhai; J.J. Gilchrist; C. Bellenguez; C. Freeman; G. Band; S.J. Bumpstead; S. Edkins; E. Giannoulatou; E. Gray; S. Dronov; S.E. Hunt; C. Langford; R.D. Pearson; Z. Su; D. Vukcevic; A.W. Macharia; S. Uyoga; C. Ndila; N. Mturi; P. Njuguna; S. Mohammed; J.A. Berkley; I. Mwangi; S. Mwarumba; B.S. Kitsao; B.S. Lowe; S.C. Morpeth; I. Khandwalla; Jenefer Blackwell; E. Bramon; M.A. Brown; J.P. Casas; A. Corvin; A. Duncanson; J. Jankowski; H.S. Markus; C.G. Mathew; C.N.A. Palmer; R. Plomin; S.J. Sawcer; R.C. Trembath; A.C. Viswanathan; N.W. Wood; P. Deloukas; L. Peltonen; T.N. Williams; J.A.G. Scott; S.J. Chapman; P. Donnelly; A.V.S. Hill; C.C.A. Spencer

doi:10.1016/j.ajhg.2016.03.025

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

A. Rautanen, M. Pirinen, T.C. Mills, K.A. Rockett, A. Strange, A.W. Ndungu, V. Naranbhai, J.J. Gilchrist, C. Bellenguez, C. Freeman, G. Band, S.J. Bumpstead, S. Edkins, E. Giannoulatou, E. Gray, S. Dronov, S.E. Hunt, C. Langford, R.D. Pearson, Z. SuD. Vukcevic, A.W. Macharia, S. Uyoga, C. Ndila, N. Mturi, P. Njuguna, S. Mohammed, J.A. Berkley, I. Mwangi, S. Mwarumba, B.S. Kitsao, B.S. Lowe, S.C. Morpeth, I. Khandwalla, Jenefer Blackwell, E. Bramon, M.A. Brown, J.P. Casas, A. Corvin, A. Duncanson, J. Jankowski, H.S. Markus, C.G. Mathew, C.N.A. Palmer, R. Plomin, S.J. Sawcer, R.C. Trembath, A.C. Viswanathan, N.W. Wood, P. Deloukas, L. Peltonen, T.N. Williams, J.A.G. Scott, S.J. Chapman, P. Donnelly, A.V.S. Hill, C.C.A. Spencer

UWA Centre for Child Health Research (affiliated with the The Kids Research Institute Australia)

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Abstract

© 2016 The Authors.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
DOIs	https://doi.org/10.1016/j.ajhg.2016.03.025
Publication status	Published - 2 Jun 2016

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10.1016/j.ajhg.2016.03.025

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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., ... Spencer, C. C. A. (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

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

abstract = "{\textcopyright} 2016 The Authors.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.",

author = "A. Rautanen and M. Pirinen and T.C. Mills and K.A. Rockett and A. Strange and A.W. Ndungu and V. Naranbhai and J.J. Gilchrist and C. Bellenguez and C. Freeman and G. Band and S.J. Bumpstead and S. Edkins and E. Giannoulatou and E. Gray and S. Dronov and S.E. Hunt and C. Langford and R.D. Pearson and Z. Su and D. Vukcevic and A.W. Macharia and S. Uyoga and C. Ndila and N. Mturi and P. Njuguna and S. Mohammed and J.A. Berkley and I. Mwangi and S. Mwarumba and B.S. Kitsao and B.S. Lowe and S.C. Morpeth and I. Khandwalla and Jenefer Blackwell and E. Bramon and M.A. Brown and J.P. Casas and A. Corvin and A. Duncanson and J. Jankowski and H.S. Markus and C.G. Mathew and C.N.A. Palmer and R. Plomin and S.J. Sawcer and R.C. Trembath and A.C. Viswanathan and N.W. Wood and P. Deloukas and L. Peltonen and T.N. Williams and J.A.G. Scott and S.J. Chapman and P. Donnelly and A.V.S. Hill and C.C.A. Spencer",

year = "2016",

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

language = "English",

volume = "98",

pages = "1092--1100",

journal = "American Journal of Human Genetics",

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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, J, 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 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, A.

AU - Pirinen, M.

AU - Mills, T.C.

AU - Rockett, K.A.

AU - Strange, A.

AU - Ndungu, A.W.

AU - Naranbhai, V.

AU - Gilchrist, J.J.

AU - Bellenguez, C.

AU - Freeman, C.

AU - Band, G.

AU - Bumpstead, S.J.

AU - Edkins, S.

AU - Giannoulatou, E.

AU - Gray, E.

AU - Dronov, S.

AU - Hunt, S.E.

AU - Langford, C.

AU - Pearson, R.D.

AU - Su, Z.

AU - Vukcevic, D.

AU - Macharia, A.W.

AU - Uyoga, S.

AU - Ndila, C.

AU - Mturi, N.

AU - Njuguna, P.

AU - Mohammed, S.

AU - Berkley, J.A.

AU - Mwangi, I.

AU - Mwarumba, S.

AU - Kitsao, B.S.

AU - Lowe, B.S.

AU - Morpeth, S.C.

AU - Khandwalla, I.

AU - Blackwell, Jenefer

AU - Bramon, E.

AU - Brown, M.A.

AU - Casas, J.P.

AU - Corvin, A.

AU - Duncanson, A.

AU - Jankowski, J.

AU - Markus, H.S.

AU - Mathew, C.G.

AU - Palmer, C.N.A.

AU - Plomin, R.

AU - Sawcer, S.J.

AU - Trembath, R.C.

AU - Viswanathan, A.C.

AU - Wood, N.W.

AU - Deloukas, P.

AU - Peltonen, L.

AU - Williams, T.N.

AU - Scott, J.A.G.

AU - Chapman, S.J.

AU - Donnelly, P.

AU - Hill, A.V.S.

AU - Spencer, C.C.A.

PY - 2016/6/2

Y1 - 2016/6/2

N2 - © 2016 The Authors.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 - © 2016 The Authors.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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