Common variants in the HLA-DRB1-HLA-DQA1 HLA class II region are associated with susceptibility to visceral leishmaniasis

Michaela Fakiola; Amy Strange; Heather J. Cordell; E. Nancy Miller; Matti Pirinen; Zhan Su; Anshuman Mishra; Sanjana Mehrotra; Gloria R. Monteiro; Gavin Band; Celine Bellenguez; Serge Dronov; Sarah Edkins; Colin Freeman; Eleni Giannoulatou; Emma Gray; Sarah E. Hunt; Henio G. Lacerda; Cordelia Langford; Richard Pearson; Nubia N. Pontes; Madhukar Rai; Shri P. Singh; Linda Smith; Olivia Sousa; Damjan Vukcevic; 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; Anna Rautanen; Stephen J. Sawcer; Richard C. Trembath; Ananth C. Viswanathan; Nicholas W. Wood; Mary E. Wilson; Panos Deloukas; Leena Peltonen; Frank Christiansen; Campbell Witt; Selma M. B. Jeronimo; Shyam Sundar; Chris C. A. Spencer; Jenefer M. Blackwell; Peter Donnelly; Wellcome Trust Case Control

doi:10.1038/ng.2518

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Common variants in the HLA-DRB1-HLA-DQA1 HLA class II region are associated with susceptibility to visceral leishmaniasis

Journal article

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Common variants in the HLA-DRB1-HLA-DQA1 HLA class II region are associated with susceptibility to visceral leishmaniasis

Michaela Fakiola, Amy Strange, Heather J. Cordell, E. Nancy Miller, Matti Pirinen, Zhan Su, Anshuman Mishra, Sanjana Mehrotra, Gloria R. Monteiro, Gavin Band, …

Nature genetics, Vol.45(2), pp.208-213

01/02/2013

DOI: https://doi.org/10.1038/ng.2518

PMID: 23291585

Abstract

Genetics & Heredity

Life Sciences & Biomedicine

Science & Technology

To identify susceptibility loci for visceral leishmaniasis, we undertook genome-wide association studies in two populations: 989 cases and 1,089 controls from India and 357 cases in 308 Brazilian families (1,970 individuals). The HLA-DRB1-HLA-DQA1 locus was the only region to show strong evidence of association in both populations. Replication at this region was undertaken in a second Indian population comprising 941 cases and 990 controls, and combined analysis across the three cohorts for rs9271858 at this locus showed P-combined = 2.76 x 10(-17) and odds ratio (OR) = 1.41, 95% confidence interval (Cl) = 1.30-1.52. A conditional analysis provided evidence for multiple associations within the HLA-DRB1-HLA-DQA1 region, and a model in which risk differed between three groups of haplotypes better explained the signal and was significant in the Indian discovery and replication cohorts. In conclusion, the HLA-DRB1-HLA-DQA1 HLA class II region contributes to visceral leishmaniasis susceptibility in India and Brazil, suggesting shared genetic risk factors for visceral leishmaniasis that cross the epidemiological divides of geography and parasite species.

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Title: Common variants in the HLA-DRB1-HLA-DQA1 HLA class II region are associated with susceptibility to visceral leishmaniasis
Creators - without role: Michaela Fakiola - University of Cambridge
Amy Strange
Heather J. Cordell - Newcastle University
E. Nancy Miller - University of Cambridge
Matti Pirinen - University of Oxford
Zhan Su - University of Oxford
Anshuman Mishra - Banaras Hindu University
Sanjana Mehrotra - Banaras Hindu University
Gloria R. Monteiro - Univ Fed Rio Grande do Norte, Dept Biochem, Ctr Biosci, BR-59072970 Natal, RN, Brazil
Gavin Band - University of Oxford
Celine Bellenguez - University of Oxford
Serge Dronov - Wellcome Sanger Institute
Sarah Edkins - Wellcome Sanger Institute
Colin Freeman - University of Oxford
Eleni Giannoulatou - University of Oxford
Emma Gray - Wellcome Sanger Institute
Sarah E. Hunt - Wellcome Sanger Institute
Henio G. Lacerda - Univ Fed Rio Grande do Norte, Dept Infect Dis, BR-59072970 Natal, RN, Brazil
Cordelia Langford - Wellcome Sanger Institute
Richard Pearson - University of Oxford
Nubia N. Pontes - Univ Fed Rio Grande do Norte, Dept Biochem, Ctr Biosci, BR-59072970 Natal, RN, Brazil
Madhukar Rai - Banaras Hindu University
Shri P. Singh - Banaras Hindu University
Linda Smith - Royal Perth Hosp, Dept Clin Immunol, Perth, WA 6001, Australia
Olivia Sousa - Univ Fed Rio Grande do Norte, Dept Biochem, Ctr Biosci, BR-59072970 Natal, RN, Brazil
Damjan Vukcevic - University of Oxford
Elvira Bramon - HLT
Matthew A. Brown - University of Queensland
Juan P. Casas - Supreme Council Of Health
Aiden Corvin - College Station Medical Center
Audrey Duncanson - Wellcome Trust
Janusz Jankowski - University of Oxford
Hugh S. Markus - University of London
Christopher G. Mathew - Supreme Council Of Health
Colin N. A. Palmer - University of Dundee
Robert Plomin - Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr, London WC2R 2LS, England
Anna Rautanen - University of Oxford
Stephen J. Sawcer - University of Cambridge
Richard C. Trembath - Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab ICDEM, Oxford OX3 7LJ, England
Ananth C. Viswanathan - Moorfields Eye Hosp NHS Fdn Trust, NIHR Biomed Ctr Ophthalmol, London, England
Nicholas W. Wood - Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England
Mary E. Wilson - University of Iowa
Panos Deloukas - Wellcome Sanger Institute
Leena Peltonen - Wellcome Sanger Institute
Frank Christiansen - Royal Perth Hosp, Dept Clin Immunol, Perth, WA 6001, Australia
Campbell Witt - Royal Perth Hosp, Dept Clin Immunol, Perth, WA 6001, Australia
Selma M. B. Jeronimo - Federal Reserve
Shyam Sundar - Banaras Hindu University
Chris C. A. Spencer - University of Oxford
Jenefer M. Blackwell - University of Cambridge
Peter Donnelly - University of Oxford
Wellcome Trust Case Control
Publication Details: Nature genetics, Vol.45(2), pp.208-213
Publisher: Springer Nature
Number of pages: 6
Grant note: 085475/Z/08/Z; 074196/Z/04/Z / Wellcome Trust 085475/B/08/Z; 085475/Z/08/Z / Wellcome Trust, WTCCC2 project 087436/Z/10/Z / Wellcome Senior Fellowship in Basic Biomedical Science; Wellcome Trust P50AI074321; P50 AI-30639; 1201 AI076233; R01 AI048822 / US National Institutes of Health (Tropical Medicine Research Center) in Brazil; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA NF-SI-0507-10379 / National Institute for Health Research; National Institute for Health Research (NIHR) MC_G1000735; G9817803B / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) 090532/Z/09/Z; 075491/Z/04/B / Wellcome Trust Centre for Human Genetics core grants MC_G1000735 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) Royal Society Wolfson Merit Award; Royal Society
Identifiers: 9935133208331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article