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

Lam C. Tsoi, Philip E. Stuart, Chao Tian, Johann E. Gudjonsson, Sayantan Das, Matthew Zawistowski, Eva Ellinghaus, Jonathan N. Barker, Vinod Chandran, Nick Dand, Kristina Callis Duffin, Charlotta Enerbäck, Tõnu Esko, Andre Franke, Dafna D. Gladman, Per Hoffmann, Külli Kingo, Sulev Kõks, Gerald G. Krueger, Henry W. Lim, Andres Metspalu, Ulrich Mrowietz, Sören Mucha, Proton Rahman, Andre Reis, Trilokraj Tejasvi, Richard Trembath, John J. Voorhees, Stephan Weidinger, Michael Weichenthal, Xiaoquan Wen, Nicholas Eriksson, Hyun M. Kang, David A. Hinds, Rajan P. Nair, Gonçalo R. Abecasis and James T Elder ()
Additional contact information
Lam C. Tsoi: University of Michigan Medical School
Philip E. Stuart: University of Michigan Medical School
Chao Tian: 23andMe, Inc., Mountain View
Johann E. Gudjonsson: University of Michigan Medical School
Sayantan Das: Center for Statistical Genetics, University of Michigan
Matthew Zawistowski: Center for Statistical Genetics, University of Michigan
Eva Ellinghaus: Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel
Jonathan N. Barker: St John's Institute of Dermatology, Faculty of Life Sciences and Medicine, King's College London
Vinod Chandran: University of Toronto
Nick Dand: St John's Institute of Dermatology, Faculty of Life Sciences and Medicine, King's College London
Kristina Callis Duffin: University of Utah
Charlotta Enerbäck: Linköping University
Tõnu Esko: Estonian Genome Center, University of Tartu
Andre Franke: Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel
Dafna D. Gladman: University of Toronto
Per Hoffmann: Institute of Human Genetics, University of Bonn
Külli Kingo: Dermatology Clinic, Tartu University Hospital, University of Tartu
Sulev Kõks: Centre of Translational Medicine and Centre for Translational Genomics, University of Tartu
Gerald G. Krueger: University of Utah
Henry W. Lim: Henry Ford Hospital
Andres Metspalu: Estonian Genome Center, University of Tartu
Ulrich Mrowietz: University Medical Center Schleswig-Holstein, Campus Kiel
Sören Mucha: Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel
Proton Rahman: Memorial University, St. John's
Andre Reis: Institute of Human Genetics, FAU Erlangen-Nürnberg
Trilokraj Tejasvi: University of Michigan Medical School
Richard Trembath: King’s College London
John J. Voorhees: University of Michigan Medical School
Stephan Weidinger: University Medical Center Schleswig-Holstein, Campus Kiel
Michael Weichenthal: University Medical Center Schleswig-Holstein, Campus Kiel
Xiaoquan Wen: Center for Statistical Genetics, University of Michigan
Nicholas Eriksson: 23andMe, Inc., Mountain View
Hyun M. Kang: Center for Statistical Genetics, University of Michigan
David A. Hinds: 23andMe, Inc., Mountain View
Rajan P. Nair: University of Michigan Medical School
Gonçalo R. Abecasis: Center for Statistical Genetics, University of Michigan
James T Elder: University of Michigan Medical School

Nature Communications, 2017, vol. 8, issue 1, 1-8

Abstract: 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.

Date: 2017
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DOI: 10.1038/ncomms15382

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