| Common variants in the HLA-DRB1-HLA-DQA1 HLA class II region are associated with susceptibility to visceral leishmaniasis. | |
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MedLine Citation:
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PMID: 23291585 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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; ; 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 Pearson; Núbia N Pontes; Madhukar Rai; Shri P Singh; Linda Smith; Olivia Sousa; Damjan Vukcevic; Elvira Bramon; Matthew A Brown; Juan P Casas; Aiden Corvin; Audrey Duncanson; Janusz Jankowski; Hugh S Markus; Christopher G 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; Peter Donnelly |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2013-01-06 |
Journal Detail:
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Title: Nature genetics Volume: 45 ISSN: 1546-1718 ISO Abbreviation: Nat. Genet. Publication Date: 2013 Feb |
Date Detail:
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Created Date: 2013-01-29 Completed Date: 2013-03-26 Revised Date: 2013-05-20 |
Medline Journal Info:
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Nlm Unique ID: 9216904 Medline TA: Nat Genet Country: United States |
Other Details:
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Languages: eng Pagination: 208-13 Citation Subset: IM |
Affiliation:
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Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, UK. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Brazil Electrophoresis, Agar Gel Gene Frequency Genetic Predisposition to Disease / genetics* Genome-Wide Association Study Genotype HLA-DQ alpha-Chains / genetics* HLA-DRB1 Chains / genetics* Haplotypes / genetics Humans India Leishmaniasis, Visceral / genetics* Linear Models Odds Ratio Oligonucleotide Array Sequence Analysis Polymorphism, Single Nucleotide / genetics |
| Grant Support | |
ID/Acronym/Agency:
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074196/Z/04/Z//Wellcome Trust; 075491/Z/04/B//Wellcome Trust; 085475/B/08/Z//Wellcome Trust; 085475/Z/08/Z//Wellcome Trust; 087436/Z/10/Z//Wellcome Trust; 089698//Wellcome Trust; 090532/Z/09/Z//Wellcome Trust; 097364/Z/11/Z//Wellcome Trust; P50 AI-30639/AI/NIAID NIH HHS; P50AI074321/AI/NIAID NIH HHS; R01 AI048822/AI/NIAID NIH HHS; R01 AI048822/AI/NIAID NIH HHS; R01 AI076233/AI/NIAID NIH HHS; R01 AI076233/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/HLA-DQ alpha-Chains; 0/HLA-DQA1 antigen; 0/HLA-DRB1 Chains |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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