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