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

Rajan P. Nair, Kristina Callis Duffin, 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 LiaoPui 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

Research output: Contribution to journalArticle

906 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)199-204
Number of pages6
JournalNature genetics
Volume41
Issue number2
DOIs
StatePublished - Feb 2009

ASJC Scopus subject areas

  • Genetics

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    Nair, R. P., Duffin, K. C., Helms, C., Ding, J., Stuart, P. E., Goldgar, D., Gudjonsson, J. E., Li, Y., Tejasvi, T., Feng, B. J., Ruether, A., Schreiber, S., Weichenthal, M., Gladman, D., Rahman, P., Schrodi, S. J., Prahalad, S., Guthery, S. L., Fischer, J., ... Abecasis, G. R. (2009). Genome-wide scan reveals association of psoriasis with IL-23 and NF-κB pathways. Nature genetics, 41(2), 199-204. https://doi.org/10.1038/ng.311