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

Fakiola, M., Strange, A., Cordell, H. J., Miller, E. N., Pirinen, M., Su, Z., Mishra, A., Mehrotra, S., Monteiro, G. R., Band, G., Bellenguez, C., Dronov, S., Edkins, S., Freeman, C., Giannoulatou, E., Gray, E., Hunt, S. E., Lacerda, H. G., Langford, C., Pearson, R., Pontes, N. N., Rai, M., Singh, S. P., Smith, L., Sousa, O., Vukcevic, D., Bramon, E., Brown, M. A., Casas, J. P., Corvin, A., Duncanson, A., Jankowski, J., Markus, H. S., Mathew, C. G., Palmer, C. N. A., Plomin, R., Rautanen, A., Sawcer, S. J., Trembath, R. C., Viswanathan, A. C., Wood, N. W., Wilson, M. E., Deloukas, P., Peltonen, L., Christiansen, F., Witt, C., Jeronimo, S. M. B., Sundar, S., Spencer, C. C. A., Blackwell, J. M., & Donnelly, P. (2013) Common variants in the HLA-DRB1-HLA-DQA1 HLA class II region are associated with susceptibility to visceral leishmaniasis. Nature Genetics, 45(2), pp. 208-213.

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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. © 2013 Nature America, Inc. All rights reserved.

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ID Code: 89289
Item Type: Journal Article
Refereed: Yes
Additional Information: Cited By :22
Export Date: 21 September 2015
Correspondence Address: Blackwell, J.M.; Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, United Kingdom; email:
Keywords: CCL1 chemokine, chemokine receptor CXCR1, chemokine receptor CXCR2, HLA antigen class 2, HLA DQA1 antigen, HLA DRB1 antigen, interleukin 2 receptor beta, allele, article, Brazil, genetic association, genetic risk, genetic susceptibility, genetic variability, genotype, haplotype, human, India, major clinical study, priority journal, single nucleotide polymorphism, visceral leishmaniasis, Electrophoresis, Agar Gel, Gene Frequency, Genetic Predisposition to Disease, Genome-Wide Association Study, Haplotypes, HLA-DQ alpha-Chains, HLA-DRB1 Chains, Humans, Leishmaniasis, Visceral, Linear Models, Odds Ratio, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide
DOI: 10.1038/ng.2518
ISSN: 1061-4036
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: 2013 Nature America Inc
Deposited On: 20 Oct 2015 01:56
Last Modified: 19 Feb 2016 03:26

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