Variation at HLA-DRB1 is associated with resistance to enteric fever

Sarah J. Dunstan; Nguyen Thi Hue; Buhm Han; Zheng Li; Trinh Thi Bich Tram; Kar Seng Sim; Christopher M. Parry; Nguyen Tran Chinh; Ha Vinh; Nguyen Phu Huong Lan; Nga Tran Vu Thieu; Phat Voong Vinh; Samir Koirala; Sabina Dongol; Amit Arjyal; Abhilasha Karkey; Olita Shilpakar; Christiane Dolecek; Jia Nee Foo; Le Thi Phuong; Mai Ngoc Lanh; Tan Do; Tin Aung; Do Nu Hon; Yik Ying Teo; Martin L. Hibberd; Katherine L. Anders; Yukinori Okada; Soumya Raychaudhuri; Cameron P. Simmons; Stephen Baker; Paul I.W. De Bakker; Buddha Basnyat; Tran Tinh Hien; Jeremy J. Farrar; Chiea Chuen Khor

doi:10.1038/ng.3143

Variation at HLA-DRB1 is associated with resistance to enteric fever

Sarah J. Dunstan^*, Nguyen Thi Hue, Buhm Han, Zheng Li, Trinh Thi Bich Tram, Kar Seng Sim, Christopher M. Parry, Nguyen Tran Chinh, Ha Vinh, Nguyen Phu Huong Lan, Nga Tran Vu Thieu, Phat Voong Vinh, Samir Koirala, Sabina Dongol, Amit Arjyal, Abhilasha Karkey, Olita Shilpakar, Christiane Dolecek, Jia Nee Foo, Le Thi PhuongMai Ngoc Lanh, Tan Do, Tin Aung, Do Nu Hon, Yik Ying Teo, Martin L. Hibberd, Katherine L. Anders, Yukinori Okada, Soumya Raychaudhuri, Cameron P. Simmons, Stephen Baker, Paul I.W. De Bakker, Buddha Basnyat, Tran Tinh Hien, Jeremy J. Farrar, Chiea Chuen Khor

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

77 Citations (Scopus)

Abstract

Enteric fever affects more than 25 million people annually and results from systemic infection with Salmonella enterica serovar Typhi or Paratyphi pathovars A, B or C 1. We conducted a genome-wide association study of 432 individuals with blood culture-confirmed enteric fever and 2,011 controls from Vietnam. We observed strong association at rs7765379 (odds ratio (OR) for the minor allele = 0.18, P = 4.5 × 10 â '10), a marker mapping to the HLA class II region, in proximity to HLA-DQB1 and HLA-DRB1. We replicated this association in 595 enteric fever cases and 386 controls from Nepal and also in a second independent collection of 151 cases and 668 controls from Vietnam. Imputation-based fine-mapping across the extended MHC region showed that the classical HLA-DRB1∗04:05 allele (OR = 0.14, P = 2.60 × 10 â '11) could entirely explain the association at rs7765379, thus implicating HLA-DRB1 as a major contributor to resistance against enteric fever, presumably through antigen presentation.

Original language	English
Pages (from-to)	1333-1336
Number of pages	4
Journal	Nature Genetics
Volume	46
Issue number	12
DOIs	https://doi.org/10.1038/ng.3143
Publication status	Published - Dec 11 2014
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2014 Nature America, Inc. All rights reserved.

ASJC Scopus Subject Areas

Genetics

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10.1038/ng.3143

Cite this

Dunstan, S. J., Hue, N. T., Han, B., Li, Z., Tram, T. T. B., Sim, K. S., Parry, C. M., Chinh, N. T., Vinh, H., Lan, N. P. H., Thieu, N. T. V., Vinh, P. V., Koirala, S., Dongol, S., Arjyal, A., Karkey, A., Shilpakar, O., Dolecek, C., Foo, J. N., ... Khor, C. C. (2014). Variation at HLA-DRB1 is associated with resistance to enteric fever. Nature Genetics, 46(12), 1333-1336. https://doi.org/10.1038/ng.3143

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title = "Variation at HLA-DRB1 is associated with resistance to enteric fever",

abstract = "Enteric fever affects more than 25 million people annually and results from systemic infection with Salmonella enterica serovar Typhi or Paratyphi pathovars A, B or C 1. We conducted a genome-wide association study of 432 individuals with blood culture-confirmed enteric fever and 2,011 controls from Vietnam. We observed strong association at rs7765379 (odds ratio (OR) for the minor allele = 0.18, P = 4.5 × 10 {\^a} '10), a marker mapping to the HLA class II region, in proximity to HLA-DQB1 and HLA-DRB1. We replicated this association in 595 enteric fever cases and 386 controls from Nepal and also in a second independent collection of 151 cases and 668 controls from Vietnam. Imputation-based fine-mapping across the extended MHC region showed that the classical HLA-DRB1∗04:05 allele (OR = 0.14, P = 2.60 × 10 {\^a} '11) could entirely explain the association at rs7765379, thus implicating HLA-DRB1 as a major contributor to resistance against enteric fever, presumably through antigen presentation.",

author = "Dunstan, {Sarah J.} and Hue, {Nguyen Thi} and Buhm Han and Zheng Li and Tram, {Trinh Thi Bich} and Sim, {Kar Seng} and Parry, {Christopher M.} and Chinh, {Nguyen Tran} and Ha Vinh and Lan, {Nguyen Phu Huong} and Thieu, {Nga Tran Vu} and Vinh, {Phat Voong} and Samir Koirala and Sabina Dongol and Amit Arjyal and Abhilasha Karkey and Olita Shilpakar and Christiane Dolecek and Foo, {Jia Nee} and Phuong, {Le Thi} and Lanh, {Mai Ngoc} and Tan Do and Tin Aung and Hon, {Do Nu} and Teo, {Yik Ying} and Hibberd, {Martin L.} and Anders, {Katherine L.} and Yukinori Okada and Soumya Raychaudhuri and Simmons, {Cameron P.} and Stephen Baker and {De Bakker}, {Paul I.W.} and Buddha Basnyat and Hien, {Tran Tinh} and Farrar, {Jeremy J.} and Khor, {Chiea Chuen}",

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Dunstan, SJ, Hue, NT, Han, B, Li, Z, Tram, TTB, Sim, KS, Parry, CM, Chinh, NT, Vinh, H, Lan, NPH, Thieu, NTV, Vinh, PV, Koirala, S, Dongol, S, Arjyal, A, Karkey, A, Shilpakar, O, Dolecek, C, Foo, JN, Phuong, LT, Lanh, MN, Do, T, Aung, T, Hon, DN, Teo, YY, Hibberd, ML, Anders, KL, Okada, Y, Raychaudhuri, S, Simmons, CP, Baker, S, De Bakker, PIW, Basnyat, B, Hien, TT, Farrar, JJ & Khor, CC 2014, 'Variation at HLA-DRB1 is associated with resistance to enteric fever', Nature Genetics, vol. 46, no. 12, pp. 1333-1336. https://doi.org/10.1038/ng.3143

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AU - Dunstan, Sarah J.

AU - Hue, Nguyen Thi

AU - Han, Buhm

AU - Li, Zheng

AU - Tram, Trinh Thi Bich

AU - Sim, Kar Seng

AU - Parry, Christopher M.

AU - Chinh, Nguyen Tran

AU - Vinh, Ha

AU - Lan, Nguyen Phu Huong

AU - Thieu, Nga Tran Vu

AU - Vinh, Phat Voong

AU - Koirala, Samir

AU - Dongol, Sabina

AU - Arjyal, Amit

AU - Karkey, Abhilasha

AU - Shilpakar, Olita

AU - Dolecek, Christiane

AU - Foo, Jia Nee

AU - Phuong, Le Thi

AU - Lanh, Mai Ngoc

AU - Do, Tan

AU - Aung, Tin

AU - Hon, Do Nu

AU - Teo, Yik Ying

AU - Hibberd, Martin L.

AU - Anders, Katherine L.

AU - Okada, Yukinori

AU - Raychaudhuri, Soumya

AU - Simmons, Cameron P.

AU - Baker, Stephen

AU - De Bakker, Paul I.W.

AU - Basnyat, Buddha

AU - Hien, Tran Tinh

AU - Farrar, Jeremy J.

AU - Khor, Chiea Chuen

PY - 2014/12/11

Y1 - 2014/12/11

N2 - Enteric fever affects more than 25 million people annually and results from systemic infection with Salmonella enterica serovar Typhi or Paratyphi pathovars A, B or C 1. We conducted a genome-wide association study of 432 individuals with blood culture-confirmed enteric fever and 2,011 controls from Vietnam. We observed strong association at rs7765379 (odds ratio (OR) for the minor allele = 0.18, P = 4.5 × 10 â '10), a marker mapping to the HLA class II region, in proximity to HLA-DQB1 and HLA-DRB1. We replicated this association in 595 enteric fever cases and 386 controls from Nepal and also in a second independent collection of 151 cases and 668 controls from Vietnam. Imputation-based fine-mapping across the extended MHC region showed that the classical HLA-DRB1∗04:05 allele (OR = 0.14, P = 2.60 × 10 â '11) could entirely explain the association at rs7765379, thus implicating HLA-DRB1 as a major contributor to resistance against enteric fever, presumably through antigen presentation.

AB - Enteric fever affects more than 25 million people annually and results from systemic infection with Salmonella enterica serovar Typhi or Paratyphi pathovars A, B or C 1. We conducted a genome-wide association study of 432 individuals with blood culture-confirmed enteric fever and 2,011 controls from Vietnam. We observed strong association at rs7765379 (odds ratio (OR) for the minor allele = 0.18, P = 4.5 × 10 â '10), a marker mapping to the HLA class II region, in proximity to HLA-DQB1 and HLA-DRB1. We replicated this association in 595 enteric fever cases and 386 controls from Nepal and also in a second independent collection of 151 cases and 668 controls from Vietnam. Imputation-based fine-mapping across the extended MHC region showed that the classical HLA-DRB1∗04:05 allele (OR = 0.14, P = 2.60 × 10 â '11) could entirely explain the association at rs7765379, thus implicating HLA-DRB1 as a major contributor to resistance against enteric fever, presumably through antigen presentation.

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Variation at HLA-DRB1 is associated with resistance to enteric fever

Abstract

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