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

LC Tsoi, PE Stuart, C Tian, JE Gudjonsson… - Nature …, 2017 - nature.com
LC Tsoi, PE Stuart, C Tian, JE Gudjonsson, S Das, M Zawistowski, E Ellinghaus, JN Barker…
Nature communications, 2017nature.com
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 …
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.
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