title: Identification of multiple independent susceptibility loci in the HLA region in Behçet's disease.
abstract: Behçet's disease is an inflammatory disease characterized by recurrent oral and genital ulcers and significant organ involvement. Localizing the genetic association between HLA-B*51 and Behçet's disease and exploring additional susceptibility loci in the human leukocyte antigen (HLA) region are complicated by the strong linkage disequilibrium in this region. We genotyped 8,572 variants in the extended HLA locus and carried out imputation and meta-analysis of 24,834 variants in 2 independent Behçet's disease cohorts from 2 ancestry groups. Genotyped SNPs were used to infer classical HLA alleles in the HLA-A, HLA-B, HLA-C, HLA-DQA1, HLA-DQB1 and HLA-DRB1 loci. Our data suggest that the robust HLA-B*51 association in Behçet's disease is explained by a variant located between the HLA-B and MICA genes (rs116799036: odds ratio (OR) = 3.88, P = 9.42 × 10(-50)). Three additional independent genetic associations within PSORS1C1 (rs12525170: OR = 3.01, P = 3.01 × 10(-26)), upstream of HLA-F-AS1 (rs114854070: OR = 1.95, P = 7.84 × 10(-14)) and with HLA-Cw*1602 (OR = 5.38, P = 6.07 × 10(-18)) were also identified and replicated.
authors: Department of Internal Medicine, Division of Rheumatology, University of Michigan, Ann Arbor, Michigan, USA.
authors: Travis
authors: T
authors: Hughes
authors: Patrick
authors: P
authors: Coit
authors: Adam
authors: A
authors: Adler
authors: Vuslat
authors: V
authors: Yilmaz
authors: Kenan
authors: K
authors: Aksu
authors: Nursen
authors: N
authors: Düzgün
authors: Gokhan
authors: G
authors: Keser
authors: Ayse
authors: A
authors: Cefle
authors: Ayten
authors: A
authors: Yazici
authors: Andac
authors: A
authors: Ergen
authors: Erkan
authors: E
authors: Alpsoy
authors: Carlo
authors: C
authors: Salvarani
authors: Bruno
authors: B
authors: Casali
authors: Ina
authors: I
authors: Kötter
authors: Javier
authors: J
authors: Gutierrez-Achury
authors: Cisca
authors: C
authors: Wijmenga
authors: Haner
authors: H
authors: Direskeneli
authors: Güher
authors: G
authors: Saruhan-Direskeneli
authors: Amr H
authors: AH
authors: Sawalha
mesh_terms: D000483:Alleles; D001528:Behcet Syndrome / Q000235:genetics*; D002874:Chromosome Mapping; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D059949:HLA-B51 Antigen / Q000235:genetics*; D015236:HLA-C Antigens / Q000235:genetics; D006239:Haplotypes; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics
chemical_list: D059949:HLA-B51 Antigen; D015236:HLA-C Antigens; C062341:HLA-F antigens; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A; C484393:PSORS1C1 protein, human; D011506:Proteins
references: Nat Genet. 2010 Aug;42(8):698-702
references: 20622878
references: Arthritis Rheum. 2009 Oct 15;61(10):1287-96
references: 19790126
references: Nat Genet. 2010 Aug;42(8):703-6
references: 20622879
references: Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1298-303
references: 9037047
references: PLoS Genet. 2009 Jun;5(6):e1000529
references: 19543373
references: Nat Genet. 2011 Nov 06;43(12):1193-201
references: 22057235
references: Ann Rheum Dis. 2010 Apr;69(4):747-54
references: 19684014
references: Jpn J Ophthalmol. 2007 Nov-Dec;51(6):431-6
references: 18158593
references: Tissue Antigens. 2008 Oct;72(4):379-82
references: 18627572
references: Bioinformatics. 2005 Jan 15;21(2):263-5
references: 15297300
references: Clin Exp Rheumatol. 2010 Jul-Aug;28(4 Suppl 60):S39-44
references: 20868569
references: Am J Hum Genet. 2007 Sep;81(3):559-75
references: 17701901
references: Nat Genet. 2006 Aug;38(8):904-9
references: 16862161
references: Am J Hum Genet. 1999 May;64(5):1406-10
references: 10205273
references: Lancet. 1990 May 5;335(8697):1078-80
references: 1970380
references: Invest Ophthalmol Vis Sci. 2000 Nov;41(12):3702-8
references: 11053265
references: Nature. 2010 Oct 28;467(7319):1061-73
references: 20981092
references: Am J Hum Genet. 2006 May;78(5):827-851
references: 16642438
references: Tissue Antigens. 1998 Jan;51(1):111-4
references: 9459512
references: Bioinformatics. 2011 Apr 1;27(7):968-72
references: 21300701