Genome-Wide Meta-Analysis of Psoriatic Arthritis Identifies Susceptibility Locus at REL
العنوان: | Genome-Wide Meta-Analysis of Psoriatic Arthritis Identifies Susceptibility Locus at REL |
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المؤلفون: | Dafna D. Gladman, David Ellinghaus, Proton Rahman, H.-Erich Wichmann, Sophie Debrus, Michael Weichenthal, John Verner Raelson, Andre Franke, Yanming Li, Lam C. Tsoi, Christian Gieger, Sulev Kõks, Philip E. Stuart, Stephan Weidinger, Stefan Schreiber, Külli Kingo, Majid Belouchi, Tõnu Esko, Ulrich Mrowietz, Gerald G. Krueger, Cynthia Helms, Gonçalo R. Abecasis, Anne M. Bowcock, Rajan P. Nair, Anna T Onken, Eva Ellinghaus, James T. Elder, Andres Metspalu, Trilokraj Tejasvi |
المصدر: | Journal of Investigative Dermatology Journal of Investigative Dermatology; Vol 132 The Journal of investigative dermatology J. Invest. Dermatol. 132, 1133-1140 (2012) |
بيانات النشر: | Elsevier BV, 2012. |
سنة النشر: | 2012 |
مصطلحات موضوعية: | Adult, Estonia, Canada, Adolescent, Genotype, Population, Single-nucleotide polymorphism, Genome-wide association study, Locus (genetics), Dermatology, Polymorphism, Single Nucleotide, Biochemistry, Article, Young Adult, 03 medical and health sciences, Psoriatic arthritis, 0302 clinical medicine, Germany, Humans, Medicine, Genetic Predisposition to Disease, education, Molecular Biology, 030304 developmental biology, Genetic association, 030203 arthritis & rheumatology, 0303 health sciences, education.field_of_study, business.industry, Arthritis, Psoriatic, Case-control study, Odds ratio, Cell Biology, medicine.disease, United States, 3. Good health, Case-Control Studies, Immunology, Genes, rel, business, Genome-Wide Association Study |
الوصف: | Psoriatic arthritis (PsA) is a chronic inflammatory musculoskeletal disease affecting up to 30% of psoriasis vulgaris (PsV) cases and approximately 0.25 to 1% of the general population. To identify common susceptibility loci, we performed a meta-analysis of three imputed genome-wide association studies (GWAS) on psoriasis, stratified for PsA. A total of 1,160,703 single-nucleotide polymorphisnns (SNPs) were analyzed in the discovery set consisting of 535 PsA cases and 3,432 controls from Germany, the United States, and Canada. We followed up two SNPs in 1,931 PsA cases and 6,785 controls comprising six independent replication panels from Germany, Estonia, the United States, and Canada. In the combined analysis, a genome-wide significant association was detected at 2p16 near the REL locus encoding c-Rel (rs13017599, P=1.18 x 10(-8), odds ratio (OR) =1.27, 95% confidence interval (CI)=1.18-1.35). The rs13017599 polymorphism is known to associate with rheumatoid arthritis (RA), and another SNP near REL (rs702873) was recently implicated in PsV susceptibility. However, conditional analysis indicated that rs13017599, rather than rs702873, accounts for the PsA association at REL. We hypothesize that c-Rel, as a member of the Rel/NF-kappa B family, is associated with PsA in the context of disease pathways that involve other identified PsA and PsV susceptibility genes including TNIP1, TNFAIP3, and NF kappa BIA. |
وصف الملف: | application/pdf |
تدمد: | 0022-202X |
DOI: | 10.1038/jid.2011.415 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e2af15b76b99560da32c934fa1a5fe8b |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi.dedup.....e2af15b76b99560da32c934fa1a5fe8b |
قاعدة البيانات: | OpenAIRE |
تدمد: | 0022202X |
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DOI: | 10.1038/jid.2011.415 |