Genomewide Scan Reveals Association of Psoriasis with IL-23 and NF-κB Pathways

Abstract

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 × 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-α and regulate NF-κB 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.

DOI: 10.1038/ng.311

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@inproceedings{Nair2009GenomewideSR, title={Genomewide Scan Reveals Association of Psoriasis with IL-23 and NF-κB Pathways}, author={Rajan P. Nair and Kristina Callis Duffin and Cindy Helms and Jun Ding and Philip E Stuart and David E. Goldgar and Johann Eli Gudj{\'o}nsson and Yun Li and Trilokraj Tejasvi and Bing Jian Feng and Andreas Ruether and Stefan Schreiber and Michael Weichenthal and Dafna D Gladman and Proton Rahman and Steven J. Schrodi and Sampath Prahalad and Stephen L. Guthery and J Fischer and Wilson Liao and Pui-Yan Kwok and Alan Menter and G. M. Lathrop and Carol A. Wise and Ann B. Begovich and John J . Voorhees and James T. Elder and Gerald G. Krueger and Anne M . Bowcock and Gonçalo R. Abecasis}, booktitle={Nature Genetics}, year={2009} }