Genome-wide association analysis identifies new susceptibility loci for Behçet's disease and epistasis between HLA-B*51 and ERAP1 View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-02

AUTHORS

Yohei Kirino, George Bertsias, Yoshiaki Ishigatsubo, Nobuhisa Mizuki, Ilknur Tugal-Tutkun, Emire Seyahi, Yilmaz Ozyazgan, F Sevgi Sacli, Burak Erer, Hidetoshi Inoko, Zeliha Emrence, Atilla Cakar, Neslihan Abaci, Duran Ustek, Colleen Satorius, Atsuhisa Ueda, Mitsuhiro Takeno, Yoonhee Kim, Geryl M Wood, Michael J Ombrello, Akira Meguro, Ahmet Gül, Elaine F Remmers, Daniel L Kastner

ABSTRACT

Individuals with Behçet's disease suffer from episodic inflammation often affecting the orogenital mucosa, skin and eyes. To discover new susceptibility loci for Behçet's disease, we performed a genome-wide association study (GWAS) of 779,465 SNPs with imputed genotypes in 1,209 Turkish individuals with Behçet's disease and 1,278 controls. We identified new associations at CCR1, STAT4 and KLRC4. Additionally, two SNPs in ERAP1, encoding ERAP1 p.Asp575Asn and p.Arg725Gln alterations, recessively conferred disease risk. These findings were replicated in 1,468 independent Turkish and/or 1,352 Japanese samples (combined meta-analysis P < 2 × 10(-9)). We also found evidence for interaction between HLA-B*51 and ERAP1 (P = 9 × 10(-4)). The CCR1 and STAT4 variants were associated with gene expression differences. Three risk loci shared with ankylosing spondylitis and psoriasis (the MHC class I region, ERAP1 and IL23R and the MHC class I-ERAP1 interaction), as well as two loci shared with inflammatory bowel disease (IL23R and IL10) implicate shared pathogenic pathways in the spondyloarthritides and Behçet's disease. More... »

PAGES

202

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.2520

    DOI

    http://dx.doi.org/10.1038/ng.2520

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1008881446

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/23291587


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    456 schema:name Department of Genetics, Institute for Experimental Medicine, Istanbul University, Istanbul, Turkey.
    457 Department of Internal Medicine, Division of Rheumatology, Cerrahpaşa Faculty of Medicine, Istanbul University, Istanbul, Turkey.
    458 Department of Internal Medicine, Division of Rheumatology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
    459 Department of Ophthalmology, Cerrahpaşa Faculty of Medicine, Istanbul University, Istanbul, Turkey.
    460 Department of Ophthalmology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
    461 rdf:type schema:Organization
     




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