Enhanced meta-analysis and replication studies identify five new psoriasis susceptibility loci

Tsoi, Lam C. and Spain, Sarah L. and Ellinghaus, Eva and Stuart, Philip E. and Capon, Francesca and Knight, Joanne and Tejasvi, Trilokraj and Kang, Hyun M. and Allen, Michael H. and Lambert, Sylviane and Stoll, Stefan W. and Weidinger, Stephan and Gudjonsson, Johann E. and Koks, Sulev and Kingo, Külli and Esko, Tonu and Das, Sayantan and Metspalu, Andres and Weichenthal, Michael and Enerback, Charlotta and Krueger, Gerald G. and Voorhees, John J. and Chandran, Vinod and Rosen, Cheryl F. and Rahman, Proton and Gladman, Dafna D. and Reis, Andre and Nair, Rajan P. and Franke, Andre and Barker, Jonathan N. W. N. and Abecasis, Goncalo R. and Trembath, Richard C. and Elder, James T. (2015) Enhanced meta-analysis and replication studies identify five new psoriasis susceptibility loci. Nature Communications, 6. ISSN 2041-1723

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Psoriasis is a chronic autoimmune disease with complex genetic architecture. Previous genome-wide association studies (GWAS) and a recent meta-analysis using Immunochip data have uncovered 36 susceptibility loci. Here, we extend our previous meta-analysis of European ancestry by refined genotype calling and imputation and by the addition of 5,033 cases and 5,707 controls. The combined analysis, consisting of over 15,000 cases and 27,000 controls, identifies five new psoriasis susceptibility loci at genome-wide significance (P<5 × 10(-8)). The newly identified signals include two that reside in intergenic regions (1q31.1 and 5p13.1) and three residing near PLCL2 (3p24.3), NFKBIZ (3q12.3) and CAMK2G (10q22.2). We further demonstrate that NFKBIZ is a TRAF3IP2-dependent target of IL-17 signalling in human skin keratinocytes, thereby functionally linking two strong candidate genes. These results further integrate the genetics and immunology of psoriasis, suggesting new avenues for functional analysis and improved therapies.

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Journal Article
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Nature Communications
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22 Jan 2016 13:26
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19 Sep 2023 01:30