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

Document Type

Article

Publication Date

5-24-2017

Publication Title

Nat Commun

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.

Comments

© authors, Creative Commons Attribution License

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

PubMed ID

28537254

Volume

8

First Page

15382

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