Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways by Nair Rajan P, Duffin Kristina Callis, Helms Cynthia, Ding Jun, Stuart Philip E, Goldgar David, Gudjonsson Johann E, Li Yun, Tejasvi Trilokraj, Feng Bing-Jian, Ruether Andreas, Schreiber Stefan, Weichenthal Michael, Gladman Dafna, Rahman Proton, Schrodi Steven J, Prahalad Sampath, Guthery Stephen L, Fischer Judith, Liao Wilson, Kwok Pui-Yan, Menter Alan, Lathrop G Mark, Wise Carol A, Begovich Ann B, Voorhees John J, Elder James T, Krueger Gerald G, Bowcock Anne M, Abecasis Gonçalo R, Collaborative Association Study of Psoriasis in Nature genetics (2009).

[PMID: 19169254] PubMed


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.

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