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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 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.

SUBMITTER: Tsoi LC 

PROVIDER: S-EPMC5458077 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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

Tsoi Lam C LC   Stuart Philip E PE   Tian Chao C   Gudjonsson Johann E JE   Das Sayantan S   Zawistowski Matthew M   Ellinghaus Eva E   Barker Jonathan N JN   Chandran Vinod V   Dand Nick N   Duffin Kristina Callis KC   Enerbäck Charlotta C   Esko Tõnu T   Franke Andre A   Gladman Dafna D DD   Hoffmann Per P   Kingo Külli K   Kõks Sulev S   Krueger Gerald G GG   Lim Henry W HW   Metspalu Andres A   Mrowietz Ulrich U   Mucha Sören S   Rahman Proton P   Reis Andre A   Reis Andre A   Tejasvi Trilokraj T   Trembath Richard R   Voorhees John J JJ   Weidinger Stephan S   Weichenthal Michael M   Wen Xiaoquan X   Eriksson Nicholas N   Kang Hyun M HM   Hinds David A DA   Nair Rajan P RP   Abecasis Gonçalo R GR   Elder James T JT  

Nature communications 20170524


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 ro  ...[more]

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