title: Common variants in the HLA-DRB1-HLA-DQA1 HLA class II region are associated with susceptibility to visceral leishmaniasis.
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.
authors.affiliation: Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Michaela
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authors.lastname: Fakiola
authors.forename: Amy
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authors.lastname: Strange
authors.forename: Heather J
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authors.forename: E Nancy
authors.initials: EN
authors.lastname: Miller
authors.forename: Matti
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authors.forename: Zhan
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authors.forename: Anshuman
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authors.forename: Gloria R
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authors.forename: Gavin
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authors.lastname: Edkins
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authors.lastname: Freeman
authors.forename: Eleni
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authors.forename: Emma
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authors.lastname: Gray
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authors.initials: SE
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authors.forename: Henio G
authors.initials: HG
authors.lastname: Lacerda
authors.forename: Cordelia
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authors.lastname: Langford
authors.forename: Richard
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authors.forename: Núbia N
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authors.lastname: Pontes
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authors.lastname: Rai
authors.forename: Shri P
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authors.lastname: Singh
authors.forename: Linda
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authors.lastname: Smith
authors.forename: Olivia
authors.initials: O
authors.lastname: Sousa
authors.forename: Damjan
authors.initials: D
authors.lastname: Vukcevic
authors.forename: Elvira
authors.initials: E
authors.lastname: Bramon
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Brown
authors.forename: Juan P
authors.initials: JP
authors.lastname: Casas
authors.forename: Aiden
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authors.lastname: Corvin
authors.forename: Audrey
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authors.lastname: Duncanson
authors.forename: Janusz
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authors.lastname: Jankowski
authors.forename: Hugh S
authors.initials: HS
authors.lastname: Markus
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Mathew
authors.forename: Colin N A
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authors.lastname: Palmer
authors.forename: Robert
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authors.lastname: Plomin
authors.forename: Anna
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authors.lastname: Rautanen
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Sawcer
authors.forename: Richard C
authors.initials: RC
authors.lastname: Trembath
authors.forename: Ananth C
authors.initials: AC
authors.lastname: Viswanathan
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Wood
authors.forename: Mary E
authors.initials: ME
authors.lastname: Wilson
authors.forename: Panos
authors.initials: P
authors.lastname: Deloukas
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.forename: Frank
authors.initials: F
authors.lastname: Christiansen
authors.forename: Campbell
authors.initials: C
authors.lastname: Witt
authors.forename: Selma M B
authors.initials: SM
authors.lastname: Jeronimo
authors.forename: Shyam
authors.initials: S
authors.lastname: Sundar
authors.forename: Chris C A
authors.initials: CC
authors.lastname: Spencer
authors.forename: Jenefer M
authors.initials: JM
authors.lastname: Blackwell
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authors.lastname: Donnelly
mesh_terms: D001938:Brazil; D004587:Electrophoresis, Agar Gel; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D059848:HLA-DQ alpha-Chains / Q000235:genetics*; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007194:India; D007898:Leishmaniasis, Visceral / Q000235:genetics*; D016014:Linear Models; D016017:Odds Ratio; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D059848:HLA-DQ alpha-Chains; C069050:HLA-DQA1 antigen; D059811:HLA-DRB1 Chains