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Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Beh?et's disease
Elaine F Remmers1, Fulya Cosan2, Yohei Kirino1, Michael J Ombrello1, Neslihan Abaci3, Colleen Satorius1, Julie M Le1, Barbara Yang4, Benjamin D Korman1, Aris Cakiris3, Oznur Aglar3, Zeliha Emrence3, Hulya Azakli3, Duran Ustek3, Ilknur Tugal-Tutkun5, Gulsen Akman-Demir6, Wei Chen7, Christopher I Amos7, Michael B Dizon4, Afet Akdag Kose8, Gulsevim Azizlerli8, Burak Erer2, Oliver J Brand9, Virginia G Kaklamani10, Phaedon Kaklamanis11, Eldad Ben-Chetrit12, Miles Stanford13, Farida Fortune14, Marwen Ghabra15, William E R Ollier16, Young-Hun Cho17, Dongsik Bang18, John O'Shea19, Graham R Wallace20, Massimo Gadina4, Daniel L Kastner1 & Ahmet Gül2,3
Beh?et's disease is a genetically complex disease of unknown etiology characterized by recurrent inflammatory attacks affecting the orogenital mucosa, eyes and skin. We performed a genome-wide association study with 311,459 SNPs in 1,215 individuals with Beh?et's disease (cases) and 1,278 healthy controls from Turkey. We confirmed the known association of Beh?et's disease with HLA-B*51 and identified a second, independent association within the MHC Class I region. We also identified an association at IL10 (rs1518111, P = 1.88 × 10?8). Using a meta-analysis with an additional five cohorts from Turkey, the Middle East, Europe and Asia, comprising a total of 2,430 cases and 2,660 controls, we identified associations at IL10 (rs1518111, P = 3.54 × 10?18, odds ratio = 1.45, 95% CI 1.34–1.58) and the IL23R-IL12RB2 locus (rs924080, P = 6.69 × 10?9, OR = 1.28, 95% CI 1.18–1.39). The disease-associated IL10 variant (the rs1518111 A allele) was associated with diminished mRNA expression and low protein production.
