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A Shared Genetic Signature for Common Chronic Pain Conditions and its Impact on Biopsychosocial Traits

  • Scott F. Farrell
    Correspondence
    Address reprint requests to Scott Farrell, RECOVER Injury Research Centre, The University of Queensland, Surgical, Treatment & Rehabilitation Service (STARS | Level 7), 296 Herston Rd, Herston QLD 4029, Australia.
    Affiliations
    RECOVER Injury Research Centre, The University of Queensland, Herston, Queensland, Australia

    NHMRC Centre of Research Excellence: Better Health Outcomes for Compensable Injury, The University of Queensland, Herston, Queensland, Australia

    Tess Cramond Pain & Research Centre, Royal Brisbane & Women's Hospital, Herston, Queensland, Australia
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  • Pik-Fang Kho
    Affiliations
    Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California

    Molecular Cancer Epidemiology Laboratory, Population Health Program, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia

    School of Biomedical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia
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  • Mischa Lundberg
    Affiliations
    UQ Diamantina Institute, The University of Queensland & Translational Research Institute, Woolloongabba, Queensland, Australia

    Transformational Bioinformatics, CSIRO Health & Biosecurity, North Ryde, New South Wales, Australia
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  • Adrián I. Campos
    Affiliations
    Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland, Australia

    Genetic Epidemiology Laboratory, Mental Health & Neuroscience Program, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia
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  • Miguel E. Rentería
    Affiliations
    Genetic Epidemiology Laboratory, Mental Health & Neuroscience Program, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia
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  • Rutger M.J. de Zoete
    Affiliations
    School of Allied Health Science and Practice, The University of Adelaide, Adelaide, South Australia, Australia
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  • Michele Sterling
    Affiliations
    RECOVER Injury Research Centre, The University of Queensland, Herston, Queensland, Australia

    NHMRC Centre of Research Excellence: Better Health Outcomes for Compensable Injury, The University of Queensland, Herston, Queensland, Australia
    Search for articles by this author
  • Author Footnotes
    2 Trung Thanh Ngo and Gabriel Cuéllar-Partida contributed equally to this work.
    Trung Thanh Ngo
    Footnotes
    2 Trung Thanh Ngo and Gabriel Cuéllar-Partida contributed equally to this work.
    Affiliations
    RECOVER Injury Research Centre, The University of Queensland, Herston, Queensland, Australia
    Search for articles by this author
  • Author Footnotes
    # Current address: 23andMe Inc., Sunnyvale CA, USA
    ,
    Author Footnotes
    2 Trung Thanh Ngo and Gabriel Cuéllar-Partida contributed equally to this work.
    Gabriel Cuéllar-Partida
    Footnotes
    # Current address: 23andMe Inc., Sunnyvale CA, USA
    2 Trung Thanh Ngo and Gabriel Cuéllar-Partida contributed equally to this work.
    Affiliations
    UQ Diamantina Institute, The University of Queensland & Translational Research Institute, Woolloongabba, Queensland, Australia
    Search for articles by this author
  • Author Footnotes
    # Current address: 23andMe Inc., Sunnyvale CA, USA
    2 Trung Thanh Ngo and Gabriel Cuéllar-Partida contributed equally to this work.
Published:October 13, 2022DOI:https://doi.org/10.1016/j.jpain.2022.10.005

      Highlights

      • Phenome-wide association analyses reveal shared genetic causal effects across 8 chronic pain types.
      • Across >1,400 other complex traits, a small proportion (82) were affected by chronic pain.
      • 410 and 78 traits contributed to an increased or decreased risk of chronic pain (respectively).
      • These genetically supported risk & protective factors enhance translationally targeted studies.
      • The results also provide corroborating evidence for particular treatment & prevention strategies.

      Abstract

      The multiple comorbidities & dimensions of chronic pain present a formidable challenge in disentangling its aetiology. Here, we performed genome-wide association studies of 8 chronic pain types using UK Biobank data (N =4,037–79,089 cases; N = 239,125 controls), followed by bivariate linkage disequilibrium-score regression and latent causal variable analyses to determine (respectively) their genetic correlations and genetic causal proportion (GCP) parameters with 1,492 other complex traits. We report evidence of a shared genetic signature across chronic pain types as their genetic correlations and GCP directions were broadly consistent across an array of biopsychosocial traits. Across 5,942 significant genetic correlations, 570 trait pairs could be explained by a causal association (|GCP| >0.6; 5% false discovery rate), including 82 traits affected by pain while 410 contributed to an increased risk of chronic pain (cf. 78 with a decreased risk) such as certain somatic pathologies (eg, musculoskeletal), psychiatric traits (eg, depression), socioeconomic factors (eg, occupation) and medical comorbidities (eg, cardiovascular disease). This data-driven phenome-wide association analysis has demonstrated a novel and efficient strategy for identifying genetically supported risk & protective traits to enhance the design of interventional trials targeting underlying causal factors and accelerate the development of more effective treatments with broader clinical utility.

      Perspective

      Through large-scale phenome-wide association analyses of >1,400 biopsychosocial traits, this article provides evidence for a shared genetic signature across 8 common chronic pain types. It lays the foundation for further translational studies focused on identifying causal genetic variants and pathophysiological pathways to develop novel diagnostic & therapeutic technologies and strategies.

      Key words

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