Journal article

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 Show all

Nature Genetics | NATURE PUBLISHING GROUP | Published : 2013

Abstract

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 × 10(-17) and odds ratio (OR) = 1.41, 95% confidence interval (CI) = 1.30-1.52. A conditional analysis provided evidence for multiple associations within ..

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University of Melbourne Researchers

Grants

Awarded by Wellcome Trust, WTCCC2 project


Awarded by Wellcome Senior Fellowship in Basic Biomedical Science


Awarded by Wellcome Trust Centre for Human Genetics core grants


Awarded by Wellcome Trust


Awarded by US National Institutes of Health (Tropical Medicine Research Center) in Brazil


Awarded by Medical Research Council


Awarded by National Institute for Health Research


Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES


Funding Acknowledgements

The principal funding for this study was provided by the Wellcome Trust, as part of the WTCCC2 project (085475/B/08/Z and 085475/Z/08/Z). We thank S. Bertrand, J. Bryant, S.L. Clark, J.S. Conquer, T. Dibling, J.C. Eldred, S. Gamble, C. Hind, M.L. Perez, C.R. Stribling, S. Taylor and A. Wilk of the Wellcome Trust Sanger Institute's Sample and Genotyping Facilities for technical assistance. We thank D. Davison for making available his Shellfish program for calculating principal components in large genetic data sets. C.C.A.S. is supported by a Wellcome Trust Fellowship (097364/Z/11/Z). H.J.C. is supported by a Wellcome Senior Fellowship in Basic Biomedical Science (087436/Z/10/Z). P. Donnelly is supported in part by a Royal Society Wolfson Merit Award, and work was supported in part by Wellcome Trust Centre for Human Genetics core grants 090532/Z/09/Z and 075491/Z/04/B. Collection of samples and epidemiological data, sample preparation and sequence-based HLA typing were supported by grants from the Wellcome Trust (074196/Z/04/Z and 085475/Z/08/Z to J.M.B., S.S., S.M.B.J. and M.E.W.) and the US National Institutes of Health (Tropical Medicine Research Center award P50AI074321 to S.S. in India; Tropical Medicine Research Center award P50 AI-30639 to E.M. Carvalho and S.M.B.J. in Brazil; and 1201 AI076233 to M.E.W. and J.M.B.; R01 AI048822 to MEW, S.M.B.J. and J.M.B.). We give special thanks to all subjects who contributed samples and to clinicians and field staff in India and Brazil who helped with the recruitment of study subjects.