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

by Tejasvi, Trilokraj , Tsoi, Lam C. , Stuart, Philip E. , Abecasis, Gonçalo R. , Mrowietz, Ulrich , Tian, Chao , Krueger, Gerald G. , Ellinghaus, Eva , Trembath, Richard , Dand, Nick , Das, Sayantan , Gladman, Dafna D. , Chandran, Vinod , Mucha, Sören , Weidinger, Stephan , Kang, Hyun M. , Gudjonsson, Johann E. , Zawistowski, Matthew , Nair, Rajan P. , Enerbäck, Charlotta , Franke, Andre , Duffin, Kristina Callis , Rahman, Proton , Eriksson, Nicholas , Barker, Jonathan N. , Lim, Henry W. , Weichenthal, Michael , Hinds, David A. , Reis, Andre , Esko, Tõnu , Kõks, Sulev , Voorhees, John J. , Elder, James T , Hoffmann, Per , Kingo, Külli , Wen, Xiaoquan , Metspalu, Andres

in 45/43 / 631/208/205 / 631/250/248 / 692/699/4033 / Age of Onset / Datasets / Dermatology / Disease / Gene Regulatory Networks - genetics / Gene Regulatory Networks - immunology / Genetic Loci - genetics / Genetic Predisposition to Disease / Genetics / Genome-Wide Association Study / Genomes / Health risk assessment / Hospitals / Humanities and Social Sciences / Humans / Interferons - immunology / Interferons - metabolism / Life sciences / Medicine / Meta-analysis / multidisciplinary / NF-kappa B - immunology / NF-kappa B - metabolism / Polymorphism, Single Nucleotide / Protein Interaction Maps - genetics / Protein Interaction Maps - immunology / Psoriasis / Psoriasis - genetics / Psoriasis - immunology / Sample size / Science / Science (multidisciplinary) / Signal Transduction - genetics / Signal Transduction - immunology / Skin diseases / T-Lymphocytes - immunology / T-Lymphocytes - metabolism / White People - genetics

2017

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2017

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2017

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Journal Article

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

Tejasvi, Trilokraj,

Tsoi, Lam C.,

Stuart, Philip E.,

Abecasis, Gonçalo R.,

Mrowietz, Ulrich,

Tian, Chao,

Krueger, Gerald G.,

Ellinghaus, Eva,

Trembath, Richard,

Dand, Nick,

Das, Sayantan,

Gladman, Dafna D.,

Chandran, Vinod,

Mucha, Sören,

Weidinger, Stephan,

Kang, Hyun M.,

Gudjonsson, Johann E.,

Zawistowski, Matthew,

Nair, Rajan P.,

Enerbäck, Charlotta,

Franke, Andre,

Duffin, Kristina Callis,

Rahman, Proton,

Eriksson, Nicholas,

Barker, Jonathan N.,

Lim, Henry W.,

Weichenthal, Michael,

Hinds, David A.,

Reis, Andre,

Esko, Tõnu,

Kõks, Sulev,

Voorhees, John J.,

Elder, James T,

Hoffmann, Per,

Kingo, Külli,

Wen, Xiaoquan,

Metspalu, Andres

2017

Overview

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 T H 0, T H 1 and T H 17). 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. Psoriasis is an immune-mediated skin disease with a complex genetic architecture. Here, Elder and colleagues identify 16 novel psoriasis susceptibility loci using GWAS meta-analysis with a combined effective sample size of over 39,000 individuals.

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Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio

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