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

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 NF B 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 T H 0, T H 1 and T H 17). The identified loci explain â 1/428% 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 â '89). This study provides a comprehensive layout for the genetic architecture of common variants for psoriasis.