ePrints

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

Lookup NU author(s): Professor Heather Cordell

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.

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 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.

Publication metadata

Author(s): Fakiola M, Strange A, Cordell HJ, Miller EN, Pirinen M, Su Z, Mishra A, Mehrotra S, Monteiro GR, Band G, Bellenguez C, Dronov S, Edkins S, Freeman C, Giannoulatou E, Gray E, Hunt SE, Lacerda HG, Langford C, Pearson R, Pontes NN, Rai M, Singh SP, Smith L, Sousa O, Vukcevic D, Bramon E, Brown MA, Casas JP, Corvin A, Duncanson A, Jankowski J, Markus HS, Mathew CG, Palmer CNA, Plomin R, Rautanen A, Sawcer SJ, Trembath RC, Viswanathan AC, Wood NW, Wilson ME, Deloukas P, Peltonen L, Christiansen F, Witt C, Jeronimo SMB, Sundar S, Spencer CCA, Blackwell JM, Donnelly P, LeishGEN Consortium, Wellcome Trust Case Control

Publication type: Article

Publication status: Published

Journal: Nature Genetics

Year: 2013

Volume: 45

Issue: 2

Pages: 208-213

Print publication date: 01/02/2013

ISSN (print): 1061-4036

ISSN (electronic): 1546-1718

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/ng.2518

DOI: 10.1038/ng.2518

Altmetrics

Funding

Share