title: Genome-wide meta-analysis of psoriatic arthritis identifies susceptibility locus at REL.
abstract: 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 polymorphisms (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), 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-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.
authors.affiliation: Institute of Clinical Molecular Biology, Christian-Albrechts-University Kiel, Kiel, Germany. e.ellinghaus@ikmb.uni-kiel.de
authors.forename: Eva
authors.initials: E
authors.lastname: Ellinghaus
authors.forename: Philip E
authors.initials: PE
authors.lastname: Stuart
authors.forename: David
authors.initials: D
authors.lastname: Ellinghaus
authors.forename: Rajan P
authors.initials: RP
authors.lastname: Nair
authors.forename: Sophie
authors.initials: S
authors.lastname: Debrus
authors.forename: John V
authors.initials: JV
authors.lastname: Raelson
authors.forename: Majid
authors.initials: M
authors.lastname: Belouchi
authors.forename: Trilokraj
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authors.lastname: Tejasvi
authors.forename: Yanming
authors.initials: Y
authors.lastname: Li
authors.forename: Lam C
authors.initials: LC
authors.lastname: Tsoi
authors.forename: Anna T
authors.initials: AT
authors.lastname: Onken
authors.forename: Tonu
authors.initials: T
authors.lastname: Esko
authors.forename: Andres
authors.initials: A
authors.lastname: Metspalu
authors.forename: Proton
authors.initials: P
authors.lastname: Rahman
authors.forename: Dafna D
authors.initials: DD
authors.lastname: Gladman
authors.forename: Anne M
authors.initials: AM
authors.lastname: Bowcock
authors.forename: Cynthia
authors.initials: C
authors.lastname: Helms
authors.forename: Gerald G
authors.initials: GG
authors.lastname: Krueger
authors.forename: Sulev
authors.initials: S
authors.lastname: Koks
authors.forename: Külli
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authors.lastname: Kingo
authors.forename: Christian
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authors.lastname: Gieger
authors.forename: H Erich
authors.initials: HE
authors.lastname: Wichmann
authors.forename: Ulrich
authors.initials: U
authors.lastname: Mrowietz
authors.forename: Stephan
authors.initials: S
authors.lastname: Weidinger
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Gonçalo R
authors.initials: GR
authors.lastname: Abecasis
authors.forename: James T
authors.initials: JT
authors.lastname: Elder
authors.forename: Michael
authors.initials: M
authors.lastname: Weichenthal
authors.forename: Andre
authors.initials: A
authors.lastname: Franke
mesh_terms: D000293:Adolescent; D000328:Adult; D015535:Arthritis, Psoriatic / Q000235:genetics*; D002170:Canada; D016022:Case-Control Studies; D004957:Estonia; D020573:Genes, rel / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D005858:Germany; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014481:United States; D055815:Young Adult