Genome-wide meta-analysis of Psoriatic Arthritis Identifies Susceptibility Locus at REL

Genome-wide meta-analysis of Psoriatic Arthritis Identifies Susceptibility Locus at REL

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 stu...

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Main Authors: Ellinghaus, Eva, Stuart, Philip E., Ellinghaus, David, Nair, Rajan P., Debrus, Sophie, Raelson, John V., Belouchi, Majid, Tejasvi, Trilokraj, Li, Yanming, Tsoi, Lam C., Onken, Anna T., Esko, Tonu, Metspalu, Andres, Rahman, Proton, Gladman, Dafna D., Bowcock, Anne M., Helms, Cynthia, Krueger, Gerald G., Koks, Sulev, Kingo, Külli, Gieger, Christian, Wichmann, H. Erich, Mrowietz, Ulrich, Weidinger, Stephan, Schreiber, Stefan, Abecasis, Gonçalo R., Elder, James T., Weichenthal, Michael, Franke, Andre
Format: Online
Language:English
Published: 2011
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3305829/
id pubmed-3305829
recordtype oai_dc
spelling pubmed-33058292012-10-01 Genome-wide meta-analysis of Psoriatic Arthritis Identifies Susceptibility Locus at REL Ellinghaus, Eva Stuart, Philip E. Ellinghaus, David Nair, Rajan P. Debrus, Sophie Raelson, John V. Belouchi, Majid Tejasvi, Trilokraj Li, Yanming Tsoi, Lam C. Onken, Anna T. Esko, Tonu Metspalu, Andres Rahman, Proton Gladman, Dafna D. Bowcock, Anne M. Helms, Cynthia Krueger, Gerald G. Koks, Sulev Kingo, Külli Gieger, Christian Wichmann, H. Erich Mrowietz, Ulrich Weidinger, Stephan Schreiber, Stefan Abecasis, Gonçalo R. Elder, James T. Weichenthal, Michael Franke, Andre Article 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 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=1.18×10−8, OR=1.27, 95% 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-κB family, is associated with PsA in the context of disease pathways that involve other identified PsA and PsV susceptibility genes including TNIP1, TNFAIP3 and NFκBIA. 2011-12-15 2012-04 /pmc/articles/PMC3305829/ /pubmed/22170493 http://dx.doi.org/10.1038/jid.2011.415 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Ellinghaus, Eva
Stuart, Philip E.
Ellinghaus, David
Nair, Rajan P.
Debrus, Sophie
Raelson, John V.
Belouchi, Majid
Tejasvi, Trilokraj
Li, Yanming
Tsoi, Lam C.
Onken, Anna T.
Esko, Tonu
Metspalu, Andres
Rahman, Proton
Gladman, Dafna D.
Bowcock, Anne M.
Helms, Cynthia
Krueger, Gerald G.
Koks, Sulev
Kingo, Külli
Gieger, Christian
Wichmann, H. Erich
Mrowietz, Ulrich
Weidinger, Stephan
Schreiber, Stefan
Abecasis, Gonçalo R.
Elder, James T.
Weichenthal, Michael
Franke, Andre
spellingShingle Ellinghaus, Eva
Stuart, Philip E.
Ellinghaus, David
Nair, Rajan P.
Debrus, Sophie
Raelson, John V.
Belouchi, Majid
Tejasvi, Trilokraj
Li, Yanming
Tsoi, Lam C.
Onken, Anna T.
Esko, Tonu
Metspalu, Andres
Rahman, Proton
Gladman, Dafna D.
Bowcock, Anne M.
Helms, Cynthia
Krueger, Gerald G.
Koks, Sulev
Kingo, Külli
Gieger, Christian
Wichmann, H. Erich
Mrowietz, Ulrich
Weidinger, Stephan
Schreiber, Stefan
Abecasis, Gonçalo R.
Elder, James T.
Weichenthal, Michael
Franke, Andre
Genome-wide meta-analysis of Psoriatic Arthritis Identifies Susceptibility Locus at REL
author_facet Ellinghaus, Eva
Stuart, Philip E.
Ellinghaus, David
Nair, Rajan P.
Debrus, Sophie
Raelson, John V.
Belouchi, Majid
Tejasvi, Trilokraj
Li, Yanming
Tsoi, Lam C.
Onken, Anna T.
Esko, Tonu
Metspalu, Andres
Rahman, Proton
Gladman, Dafna D.
Bowcock, Anne M.
Helms, Cynthia
Krueger, Gerald G.
Koks, Sulev
Kingo, Külli
Gieger, Christian
Wichmann, H. Erich
Mrowietz, Ulrich
Weidinger, Stephan
Schreiber, Stefan
Abecasis, Gonçalo R.
Elder, James T.
Weichenthal, Michael
Franke, Andre
author_sort Ellinghaus, Eva
title Genome-wide meta-analysis of Psoriatic Arthritis Identifies Susceptibility Locus at REL
title_short Genome-wide meta-analysis of Psoriatic Arthritis Identifies Susceptibility Locus at REL
title_full Genome-wide meta-analysis of Psoriatic Arthritis Identifies Susceptibility Locus at REL
title_fullStr Genome-wide meta-analysis of Psoriatic Arthritis Identifies Susceptibility Locus at REL
title_full_unstemmed Genome-wide meta-analysis of Psoriatic Arthritis Identifies Susceptibility Locus at REL
title_sort genome-wide meta-analysis of psoriatic arthritis identifies susceptibility locus at rel
description 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 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=1.18×10−8, OR=1.27, 95% 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-κB family, is associated with PsA in the context of disease pathways that involve other identified PsA and PsV susceptibility genes including TNIP1, TNFAIP3 and NFκBIA.
publishDate 2011
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3305829/
_version_ 1611514896762011648

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