Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants.

Authors:
Lam C Tsoi, Philip E Stuart, Chao Tian, Johann E Gudjonsson, Sayantan Das, Matthew Zawistowski, Eva Ellinghaus, Jonathan N Barker, Vinod Chandran, Nick Dand, Kristina Callis Duffin, Charlotta Enerbäck, Tõnu Esko, Andre Franke, Dafna D Gladman, Per Hoffmann, Külli Kingo, Sulev Kõks, Gerald G Krueger, Henry W Lim, Andres Metspalu, Ulrich Mrowietz, Sören Mucha, Proton Rahman, Andre Reis, Trilokraj Tejasvi, Richard Trembath, John J Voorhees, Stephan Weidinger, Michael Weichenthal, Xiaoquan Wen, Nicholas Eriksson, Hyun M Kang, David A Hinds, Rajan P Nair, Gonçalo R Abecasis, James T Elder
Year of publication:
2017
Volume:
8
Issue:
-
Issn:
2041-1723
Journal title abbreviated:
NAT COMMUN
Journal title long:
Nature communications
Impact factor:
12.124
Abstract: 
Psoriasis is a complex disease of skin with a prevalence of about 2%. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for psoriasis to date, including data from eight different Caucasian cohorts, with a combined effective sample size >39,000 individuals. We identified 16 additional psoriasis susceptibility loci achieving genome-wide significance, increasing the number of identified loci to 63 for European-origin individuals. Functional analysis highlighted the roles of interferon signalling and the NFκB cascade, and we showed that the psoriasis signals are enriched in regulatory elements from different T cells (CD8+ T-cells and CD4+ T-cells including TH0, TH1 and TH17). The identified loci explain ∼28% of the genetic heritability and generate a discriminatory genetic risk score (AUC=0.76 in our sample) that is significantly correlated with age at onset (p=2 × 10-89). This study provides a comprehensive layout for the genetic architecture of common variants for psoriasis.