Nat Commun 2017 05 24;8:15382. Epub 2017 May 24.
Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
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 T0, T1 and T17). 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). This study provides a comprehensive layout for the genetic architecture of common variants for psoriasis.