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, Céline Bellenguez, Serge Dronov, Sarah Edkins, Colin Freeman, Eleni Giannoulatou, Emma Gray, Sarah E Hunt, Henio G Lacerda, Cordelia Langford, Richard PearsonNúbia N Pontes, Madhukar Rai, Shri P Singh, Linda Smith, Olivia Sousa, Damjan Vukcevic, Elvira Bramon-Bosch, Matthew A Brown, Juan P Casas, Aiden Corvin, Audrey Duncanson, Janusz Jankowski, Hugh S Markus, Christopher 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, LeishGEN Consortium

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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 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.
Original languageEnglish
Pages (from-to)208-213
Number of pages6
JournalNature Genetics
Volume45
Issue number2
DOIs
Publication statusPublished - 1 Feb 2013

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