Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci

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초록

Ankylosing spondylitis is a common, highly heritable inflammatory arthritis affecting primarily the spine and pelvis. In addition to HLA-B*27 alleles, 12 loci have previously been identified that are associated with ankylosing spondylitis in populations of European ancestry, and 2 associated loci have been identified in Asians. In this study, we used the Illumina Immunochip microarray to perform a case-control association study involving 10,619 individuals with ankylosing spondylitis (cases) and 15,145 controls. We identified 13 new risk loci and 12 additional ankylosing spondylitis-associated haplotypes at 11 loci. Two ankylosing spondylitis-associated regions have now been identified encoding four aminopeptidases that are involved in peptide processing before major histocompatibility complex (MHC) class I presentation. Protective variants at two of these loci are associated both with reduced aminopeptidase function and with MHC class I cell surface expression.

키워드

GENOME-WIDE ASSOCIATION; DISEASE SUSCEPTIBILITY LOCI; HLA CLASS-I; T-CELL; ENDOPLASMIC-RETICULUM; GENETIC SUSCEPTIBILITY; BEHCETS-DISEASE; COMMON; ERAP1; ACTIVATION
제목
Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci
저자
Cortes, Adrian; Hadler, Johanna; Pointon, Jenny P.; Robinson, Philip C.; Karaderi, Tugce; Leo, Paul; Cremin, Katie; Pryce, Karena; Harris, Jessica; Lee, Seunghun; Joo, Kyung Bin; Shim, Seung-Cheol; Weisman, Michael; Ward, Michael; Zhou, Xiaodong; Garchon, Henri-Jean; Chiocchia, Gilles; Nossent, Johannes; Lie, Benedicte A.; Forre, Oystein; Tuomilehto, Jaakko; Laiho, Kari; Jiang, Lei; Liu, Yu; Wu, Xin; Bradbury, Linda A.; Elewaut, Dirk; Burgos-Vargas, Ruben; Stebbings, Simon; Appleton, Louise; Farrah, Claire; Lau, Jonathan; Kenna, Tony J.; Haroon, Nigil; Ferreira, Manuel A.; Yang, Jian; Mulero, Juan; Fernandez-Sueiro, Jose Luis; Gonzalez-Gay, Miguel A.; Lopez-Larrea, Carlos; Deloukas, Panos; Donnelly, Peter; Bowness, Paul; Gafney, Karl; Gaston, Hill; Gladman, Dafna D.; Rahman, Proton; Maksymowych, Walter P.; Xu, Huji; Crusius, J. Bart A.; van der Horst-Bruinsma, Irene E.; Chou, Chung-Tei; Valle-Onate, Raphael; Romero-Sanchez, Consuelo; Hansen, Inger Myrnes; Pimentel-Santos, Fernando M.; Inman, Robert D.; Videm, Vibeke; Martin, Javier; Breban, Maxime; Reveille, John D.; Evans, David M.; Kim, Tae-Hwan; Wordsworth, Bryan Paul; Brown, Matthew A.
DOI
10.1038/ng.2667
발행일
2013-07
유형
Article
저널명
Nature Genetics
권
45
호
7
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730 ~ 738