Genome-wide scan reveals association of psoriasis with IL-23 and NF-κB pathways

• DOI: 10.1038/ng.311
• Publication Date: 2009-01-25T18:27:39Z
• Authors: Rajan P Nair; Kristina Callis D...; Cynthia Helms; Jun Ding; Philip E Stuart; David Goldgar; Johann E Gudjonsson; Yun Li; Trilokraj Tejasvi; Bing-Jian Feng; Andreas Ruether; Stefan Schreiber; Michael Weichenthal; Dafna Gladman; Proton Rahman; Steven J Schrodi; Sampath Prahalad; Stephen L Guthery; Judith Fischer; Wilson Liao; Pui-Yan Kwok; Alan Menter; G Mark Lathrop; Carol A Wise; Ann B Begovich; John J Voorhees; James T Elder; Gerald G Krueger; Anne M Bowcock; Gonçalo R Abecasis
• Keywords: Adult; Male; HLA-C Antigens; Autoimmune Disease; Medical and Health Sciences; Interleukin-23; Polymorphism, Single Nucleotide; Article; Young Adult; 03 medical and health sciences; Gene Frequency; Genetics; 2.1 Biological and endogenous factors; Humans; Psoriasis; Genetic Predisposition to Disease; Aetiology; Polymorphism; Tumor Necrosis Factor alpha-Induced Protein 3; Skin; 0303 health sciences; Interleukin-13; Interleukin-12 Subunit p40; Human Genome; Intracellular Signaling Peptides and Proteins; NF-kappa B; Nuclear Proteins; Single Nucleotide; Biological Sciences; Middle Aged; 3. Good health; DNA-Binding Proteins; Case-Control Studies; Female; Interleukin-4; Collaborative Association Study of Psoriasis; Signal Transduction; Developmental Biology; Genome-Wide Association Study

Psoriasis is a common immune-mediated disorder that affects the skin, nails and joints. To identify psoriasis susceptibility loci, we genotyped 438,670 SNPs in 1,409 psoriasis cases and 1,436 controls of European ancestry. We followed up 21 promising SNPs in 5,048 psoriasis cases and 5,041 controls. Our results provide strong support for the association of at least seven genetic loci and psoriasis (each with combined P < 5 x 10(-8)). Loci with confirmed association include HLA-C, three genes involved in IL-23 signaling (IL23A, IL23R, IL12B), two genes that act downstream of TNF-alpha and regulate NF-kappaB signaling (TNIP1, TNFAIP3) and two genes involved in the modulation of Th2 immune responses (IL4, IL13). Although the proteins encoded in these loci are known to interact biologically, we found no evidence for epistasis between associated SNPs. Our results expand the catalog of genetic loci implicated in psoriasis susceptibility and suggest priority targets for study in other auto-immune disorders.