Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behçet's disease

Elaine F. Remmers, Fulya Cosan, Yohei Kirino, Michael J. Ombrello, Neslihan Abaci, Colleen Satorius, Julie M. Le, Barbara Yang, Benjamin D. Korman, Aris Cakiris, Oznur Aglar, Zeliha Emrence, Hulya Azakli, Duran Ustek, Ilknur Tugal-Tutkun, Gulsen Akman-Demir, Wei Chen, Christopher I. Amos, Michael B. Dizon, Afet Akdag KoseGulsevim Azizlerli, Burak Erer, Oliver J. Brand, Virginia G. Kaklamani, Phaedon Kaklamanis, Eldad Ben-Chetrit, Miles Stanford, Farida Fortune, Marwen Ghabra, William E.R. Ollier, Young Hun Cho, Dongsik Bang, John O'Shea, Graham R. Wallace, Massimo Gadina, Daniel L. Kastner, Ahmet Gül

Research output: Contribution to journalArticlepeer-review

438 Scopus citations

Abstract

Behçet'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 Behçet's disease (cases) and 1,278 healthy controls from Turkey. We confirmed the known association of Behçet'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.

Original languageEnglish (US)
Pages (from-to)698-702
Number of pages5
JournalNature Genetics
Volume42
Issue number8
DOIs
StatePublished - Aug 2010
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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