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

Author

Listed:
  • Lam C. Tsoi

    (University of Michigan Medical School
    Center for Statistical Genetics, University of Michigan
    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
    Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Research Institute, 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
    Broad Institute of MIT and Harvard)

  • Andre Franke

    (Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel)

  • Dafna D. Gladman

    (University of Toronto
    Centre for Prognosis Studies in the Rheumatic Diseases, Toronto Western Research Institute, University of Toronto)

  • Per Hoffmann

    (Institute of Human Genetics, University of Bonn
    University of Basel)

  • Külli Kingo

    (Dermatology Clinic, Tartu University Hospital, University of Tartu)

  • Sulev Kõks

    (Centre of Translational Medicine and Centre for Translational Genomics, University of Tartu
    Estonian University of Life Sciences)

  • 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
    Ann Arbor Veterans Affairs Hospital)

  • 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
    Ann Arbor Veterans Affairs Hospital)

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.

Suggested Citation

  • 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 & Cha, 2017. "Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants," Nature Communications, Nature, vol. 8(1), pages 1-8, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms15382
    DOI: 10.1038/ncomms15382
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    Citations

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    Cited by:

    1. Matthew T. Patrick & Qinmengge Li & Rachael Wasikowski & Nehal Mehta & Johann E. Gudjonsson & James T. Elder & Xiang Zhou & Lam C. Tsoi, 2022. "Shared genetic risk factors and causal association between psoriasis and coronary artery disease," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. Rikifumi Ohta & Yosuke Tanigawa & Yuta Suzuki & Manolis Kellis & Shinichi Morishita, 2024. "A polygenic score method boosted by non-additive models," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    3. Feiyang Ma & Olesya Plazyo & Allison C. Billi & Lam C. Tsoi & Xianying Xing & Rachael Wasikowski & Mehrnaz Gharaee-Kermani & Grace Hile & Yanyun Jiang & Paul W. Harms & Enze Xing & Joseph Kirma & Jing, 2023. "Single cell and spatial sequencing define processes by which keratinocytes and fibroblasts amplify inflammatory responses in psoriasis," Nature Communications, Nature, vol. 14(1), pages 1-19, December.

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