Journal article
Common variants in the HLA-DRB1-HLA-DQA1 HLA class II region are associated with susceptibility to visceral leishmaniasis
Nature genetics, Vol.45(2), pp.208-213
02/2013
DOI: 10.1038/ng.2518
PMCID: PMC3664012
PMID: 23291585
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.
Details
- Title: Subtitle
- Common variants in the HLA-DRB1-HLA-DQA1 HLA class II region are associated with susceptibility to visceral leishmaniasis
- Creators
- Michaela FakiolaAmy StrangeHeather J CordellMatti PirinenZhan SuE Nancy MillerAnshuman MishraSanjana MehrotraGloria R MonteiroGavin BandCéline BellenguezSerge DronovSarah EdkinsColin FreemanEleni GiannoulatouEmma GraySarah E HuntHenio G LacerdaCordelia LangfordRichard PearsonNúbia N PontesMadhukar RaiShri P SinghLinda SmithOlivia SousaDamjan VukcevicElvira BramonMatthew A BrownJuan P CasasAiden CorvinAudrey DuncansonJanusz JankowskiHugh S MarkusChristopher G MathewColin N A PalmerRobert PlominAnna RautanenStephen J SawcerRichard C TrembathAnanth C ViswanathanNicholas W WoodMary E WilsonPanos DeloukasLeena PeltonenFrank ChristiansenCampbell WittSelma M B JeronimoShyam SundarChris C A SpencerJenefer M BlackwellPeter DonnellyWellcome Trust Case Control Consortium 2
- Resource Type
- Journal article
- Publication Details
- Nature genetics, Vol.45(2), pp.208-213
- DOI
- 10.1038/ng.2518
- PMID
- 23291585
- PMCID
- PMC3664012
- NLM abbreviation
- Nat Genet
- ISSN
- 1546-1718
- eISSN
- 1546-1718
- Publisher
- United States
- Grant note
- P50 AI074321 / NIAID NIH HHS 074196/Z/04/Z / Wellcome Trust 084694 / Wellcome Trust 083948 / Wellcome Trust 075491/Z/04/B / Wellcome Trust R01 AI048822 / NIAID NIH HHS 085475/Z/08/Z / Wellcome Trust 074196 / Wellcome Trust 090532 / Wellcome Trust P50AI074321 / NIAID NIH HHS P50 AI-30639 / NIAID NIH HHS MC_G1000735 / Medical Research Council 097364/Z/11/Z / Wellcome Trust 089698 / Wellcome Trust 087436/Z/10/Z / Wellcome Trust 085475/B/08/Z / Wellcome Trust 085475 / Wellcome Trust 087436 / Wellcome Trust 095552 / Wellcome Trust R01 AI076233 / NIAID NIH HHS 090532/Z/09/Z / Wellcome Trust P50 AI030639 / NIAID NIH HHS
- Language
- English
- Date published
- 02/2013
- Academic Unit
- Microbiology and Immunology; International Programs; Epidemiology; Internal Medicine
- Record Identifier
- 9984001144402771
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