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Genome-wide association studies identify IL23R-IL12RB2 and IL10 as Behçet's disease susceptibility loci


Behçet's disease is a chronic systemic inflammatory disorder characterized by four major manifestations: recurrent ocular symptoms, oral and genital ulcers and skin lesions1. We conducted a genome-wide association study in a Japanese cohort including 612 individuals with Behçet's disease and 740 unaffected individuals (controls). We identified two suggestive associations on chromosomes 1p31.3 (IL23R-IL12RB2, rs12119179, P = 2.7 × 10−8) and 1q32.1 (IL10, rs1554286, P = 8.0 × 10−8). A meta-analysis of these two loci with results from additional Turkish and Korean cohorts showed genome-wide significant associations (rs1495965 in IL23R-IL12RB2, P = 1.9 × 10−11, odds ratio = 1.35; rs1800871 in IL10, P = 1.0 × 10−14, odds ratio = 1.45).

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Figure 1: Overview of SNPs across the HLA region in the GWAS.
Figure 2: In-depth SNP analysis in target areas.


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We sincerely thank the individuals with Behçet's disease who participated in this study. This work was supported by grants-in-aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan; a grant from the Ministry of Health, Labour and Welfare, Japan; a grant from Menicon Co., Ltd.; and a grant from the Johnson & Johnson KK Vision Care Company. The laboratory of S.B. was supported by the Agence Nationale pour la Recherche (ANR), the Fédération des Maladies Orphelines and the Association française de la maladie de Behçet.

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Authors and Affiliations



N.M. designed and supervised the experiment, provided study samples, performed data analysis and wrote the manuscript. A.M. designed the experiment, performed the SNP selection, supervised genotyping, performed data analysis, wrote the manuscript and prepared the tables and figures. M.O. participated in the experimental design, helped with data analysis and edited the manuscript. S.O. participated in the experimental design, provided study samples and edited the manuscript. T.S., T.K., N.I. and K.Y. performed genotyping. J.K. helped with data analysis. E.O., Y.W.S., E.B.L., N.K., K.N., Y.H., M.T., S.S., M.M. and Y.I. provided study samples. S.B. participated in the experimental design, helped with data analysis and participated in critical revisions of the manuscript. H.I. participated in the experimental design, provided study samples, helped with data analysis and edited the manuscript.

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Correspondence to Nobuhisa Mizuki or Hidetoshi Inoko.

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The authors declare no competing financial interests.

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Mizuki, N., Meguro, A., Ota, M. et al. Genome-wide association studies identify IL23R-IL12RB2 and IL10 as Behçet's disease susceptibility loci. Nat Genet 42, 703–706 (2010).

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