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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. [ABSTRACT FROM AUTHOR]

We carried out a meta-analysis of two recent psoriasis genome-wide association studies with a combined discovery sample of 1,831 affected individuals (cases) and 2,546 controls. One hundred and two loci selected based on P value rankings were followed up in a three-stage replication study including 4,064 cases and 4,685 controls from Michigan, Toronto, Newfoundland and Germany. In the combined meta-analysis, we identified three new susceptibility loci, including one at NOS2 (rs4795067, combined P = 4 × 10−11), one at FBXL19 (rs10782001, combined P = 9 × 10−10) and one near PSMA6-NFKBIA (rs12586317, combined P = 2 × 10−8). All three loci were also associated with psoriatic arthritis (rs4795067, combined P = 1 × 10−5; rs10782001, combined P = 4 × 10−8; and rs12586317, combined P = 6 × 10−5) and purely cutaneous psoriasis (rs4795067, combined P = 1 × 10−8; rs10782001, combined P = 2 × 10−6; and rs12586317, combined P = 1 × 10−6). We also replicated a recently identified association signal near RNF114 (rs495337, combined P = 2 × 10−7). [ABSTRACT FROM AUTHOR]