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.
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Acknowledgements
We gratefully acknowledge funding from the National Institutes of Health, the Foundation for NIH's Genetic Association Information Network and the National Psoriasis Foundation. Analysis and genotyping of follow-up samples was also supported by the German National Genome Research Network (BMFT 01GS 0171/BMBF NUW-S23T10) and POPGEN Biobank (BMBF 01GR0468), by the Canadian Institute of Health Research and the Arthritis Society of Canada, by the Centre National de Génotypage, Généthon and the Association Française contre les Myopathies (AFM), and by Celera Corporation.
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J.T.E., G.G.K., A.M.B. and G.R.A. designed and directed the study. J.D., C.H., P.E.S., D. Goldgar, B.J.F., Y.L. and G.R.A. designed and carried out the main genome scan analysis. R.P.N., K.C.D., C.H., J.D., P.E.S., J.E.G., T.T., S.P., S.L.G., W.L., P.-Y.K., A.M., C.A.W., J.J.V., J.T.E, G.G.K. and A.M.B. provided samples for the initial genome-wide association scan and replication and executed the experiments. A.R., S.S., M.W., D. Gladman, P.R., S.J.S., J.F., G.M.L. and A.B.B. provided additional replication data. J.D., J.T.E. and G.R.A. generated the first draft of the paper. Additional major edits were done by K.C.D., P.E.S., A.B.B., G.G.K. and A.M.B. All authors reviewed and approved the paper.
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Nair, R., Duffin, K., Helms, C. et al. Genome-wide scan reveals association of psoriasis with IL-23 and NF-κB pathways. Nat Genet 41, 199–204 (2009). https://doi.org/10.1038/ng.311
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DOI: https://doi.org/10.1038/ng.311
