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Genetic signature to provide robust risk assessment of psoriatic arthritis development in psoriasis patients

Author

Listed:
  • Matthew T. Patrick

    (University of Michigan Medical School)

  • Philip E. Stuart

    (University of Michigan Medical School)

  • Kalpana Raja

    (University of Michigan Medical School
    Morgridge Institute for Research)

  • Johann E. Gudjonsson

    (University of Michigan Medical School)

  • Trilokraj Tejasvi

    (University of Michigan Medical School
    Ann Arbor Veterans Affairs Hospital)

  • Jingjing Yang

    (Center for Statistical Genetics, University of Michigan
    Emory University School of Medicine)

  • Vinod Chandran

    (Division of Rheumatology, University of Toronto
    University of Toronto
    University of Toronto
    University of Toronto)

  • Sayantan Das

    (Center for Statistical Genetics, University of Michigan)

  • Kristina Callis-Duffin

    (University of Utah)

  • Eva Ellinghaus

    (Christian-Albrechts-University of Kiel)

  • Charlotta Enerbäck

    (Linköping University)

  • Tõnu Esko

    (University of Tartu
    Broad Institute of MIT and Harvard)

  • Andre Franke

    (Christian-Albrechts-University of Kiel)

  • Hyun M. Kang

    (Center for Statistical Genetics, University of Michigan)

  • Gerald G. Krueger

    (University of Utah)

  • Henry W. Lim

    (Department of Dermatology, Henry Ford Hospital)

  • Proton Rahman

    (Memorial University)

  • Cheryl F. Rosen

    (Division of Dermatology, Toronto Western Hospital, University of Toronto)

  • Stephan Weidinger

    (University Medical Center Schleswig-Holstein)

  • Michael Weichenthal

    (University Medical Center Schleswig-Holstein)

  • Xiaoquan Wen

    (Center for Statistical Genetics, University of Michigan)

  • John J. Voorhees

    (University of Michigan Medical School)

  • Gonçalo R. Abecasis

    (Center for Statistical Genetics, University of Michigan)

  • Dafna D. Gladman

    (Division of Rheumatology, University of Toronto
    University of Toronto
    University of Toronto)

  • Rajan P. Nair

    (University of Michigan Medical School)

  • James T. Elder

    (University of Michigan Medical School
    Ann Arbor Veterans Affairs Hospital)

  • Lam C. Tsoi

    (University of Michigan Medical School
    Center for Statistical Genetics, University of Michigan
    University of Michigan)

Abstract

Psoriatic arthritis (PsA) is a complex chronic musculoskeletal condition that occurs in ~30% of psoriasis patients. Currently, no systematic strategy is available that utilizes the differences in genetic architecture between PsA and cutaneous-only psoriasis (PsC) to assess PsA risk before symptoms appear. Here, we introduce a computational pipeline for predicting PsA among psoriasis patients using data from six cohorts with >7000 genotyped PsA and PsC patients. We identify 9 new loci for psoriasis or its subtypes and achieve 0.82 area under the receiver operator curve in distinguishing PsA vs. PsC when using 200 genetic markers. Among the top 5% of our PsA prediction we achieve >90% precision with 100% specificity and 16% recall for predicting PsA among psoriatic patients, using conditional inference forest or shrinkage discriminant analysis. Combining statistical and machine-learning techniques, we show that the underlying genetic differences between psoriasis subtypes can be used for individualized subtype risk assessment.

Suggested Citation

  • Matthew T. Patrick & Philip E. Stuart & Kalpana Raja & Johann E. Gudjonsson & Trilokraj Tejasvi & Jingjing Yang & Vinod Chandran & Sayantan Das & Kristina Callis-Duffin & Eva Ellinghaus & Charlotta En, 2018. "Genetic signature to provide robust risk assessment of psoriatic arthritis development in psoriasis patients," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06672-6
    DOI: 10.1038/s41467-018-06672-6
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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. Junyan Duan & Michelle N. Ngo & Satya Swaroop Karri & Lam C. Tsoi & Johann E. Gudjonsson & Babak Shahbaba & John Lowengrub & Bogi Andersen, 2024. "tauFisher predicts circadian time from a single sample of bulk and single-cell pseudobulk transcriptomic data," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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