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Evidence for causal effects of sleep disturbances on risk for osteoarthritis: a univariable and multivariable Mendelian randomization study

  • Author Footnotes
    a Authors share co-first authorship.
    J. Ni
    Correspondence
    Address correspondence and reprint requests to: J. Ni, Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, Anhui 230032, China. Tel.: 86-25-65161175.
    Footnotes
    a Authors share co-first authorship.
    Affiliations
    Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, Anhui 230032, China

    Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, Anhui 230032, China
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  • Author Footnotes
    a Authors share co-first authorship.
    W. Zhou
    Footnotes
    a Authors share co-first authorship.
    Affiliations
    Department of Molecular Diagnostics, Sun Yat-Sen University Cancer Centre, Guangzhou, Guangdong 510060, China
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  • H. Cen
    Affiliations
    Department of Preventive Medicine, Medical School of Ningbo University, Ningbo, Zhejiang 315211, China
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  • G. Chen
    Affiliations
    School of Health Services Management, Anhui Medical University, Hefei, Anhui 230032, China
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  • J. Huang
    Affiliations
    Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, Anhui 230032, China

    Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, Anhui 230032, China
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  • K. Yin
    Affiliations
    Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, Anhui 230032, China

    Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, Anhui 230032, China
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  • C. Sui
    Correspondence
    Address correspondence and reprint requests to: C. Sui, Department of Orthopedics Trauma, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, China.
    Affiliations
    Department of Orthopedics Trauma, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, China
    Search for articles by this author
  • Author Footnotes
    a Authors share co-first authorship.
Published:December 06, 2021DOI:https://doi.org/10.1016/j.joca.2021.11.021

      Summary

      Objective

      To disentangle whether sleep disturbances have a causal effect on the risk of osteoarthritis (OA) using genetically based approaches.

      Method

      We performed univariable and multivariable Mendelian randomization (MR) analyses using publicly released genome-wide association studies summary statistics to estimate the causal associations of sleep disturbances with OA risk. The inverse-variance weighted (IVW) method was utilized as primary MR analysis, whereas complementary methods including weighted median, weighted mode, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO) were applied to detect and correct for the presence of pleiotropy.

      Results

      There were 228 independent instrumental variables (IVs) for insomnia and 78, 27 and 8 IVs for sleep duration, short sleep duration and long sleep duration, respectively. Univariable MR analysis suggested that genetically determined insomnia or short sleep duration exerted a causal effect on overall OA in an unfavorable manner (Insomnia: OR = 1.22, 95%CI = 1.15–1.30, P = 8.05 × 10−10; Short sleep duration: OR = 1.04, 95%CI = 1.02–1.07, P = 2.20 × 10−3). More compelling, increasing genetic liability to insomnia or short sleep duration was also associated with OA risk, after accounting for effects of insomnia or short sleep duration on body mass index, type 2 diabetes and depression individually, and in a combined model considering all three confounders.

      Conclusions

      Findings suggested consisted evidence for an adverse effect of increased insomnia or short sleep duration on OA risk. Strategies to mitigate sleep disturbances may be one of the cornerstones protects against OA.

      Keywords

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