Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants.
Tsoi L, Stuart P, Tian C, Gudjonsson J, Das S, Zawistowski M, Ellinghaus E, Barker J, Chandran V, Dand N, Duffin K, Enerbäck C, Esko T, Franke A, Gladman D, Hoffmann P, Kingo K, Kõks S, Krueger G, Lim H, Metspalu A, Mrowietz U, Mucha S, Rahman P, Reis A, Tejasvi T, Trembath R, Voorhees J, Weidinger S, Weichenthal M, Wen X, Eriksson N, Kang H, Hinds D, Nair R, Abecasis G, Elder J. Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants.. Nat Commun 2017; 8:15382.
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.
Medical Subject Headings
Age of Onset; European Continental Ancestry Group; Gene Regulatory Networks; Genetic Loci; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Interferons; NF-kappa B; Polymorphism, Single Nucleotide; Protein Interaction Maps; Psoriasis; Signal Transduction; T-Lymphocytes