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A genome-wide meta-analysis identifies 50 genetic loci associated with carpal tunnel syndrome

Author

Listed:
  • Astros Th. Skuladottir

    (deCODE genetics/Amgen Inc.)

  • Gyda Bjornsdottir

    (deCODE genetics/Amgen Inc.)

  • Egil Ferkingstad

    (deCODE genetics/Amgen Inc.)

  • Gudmundur Einarsson

    (deCODE genetics/Amgen Inc.)

  • Lilja Stefansdottir

    (deCODE genetics/Amgen Inc.)

  • Muhammad Sulaman Nawaz

    (deCODE genetics/Amgen Inc.
    University of Iceland)

  • Asmundur Oddsson

    (deCODE genetics/Amgen Inc.)

  • Thorunn A. Olafsdottir

    (deCODE genetics/Amgen Inc.)

  • Saedis Saevarsdottir

    (deCODE genetics/Amgen Inc.
    University of Iceland
    Landspitali—the National University Hospital of Iceland)

  • G. Bragi Walters

    (deCODE genetics/Amgen Inc.
    University of Iceland)

  • Sigurdur H. Magnusson

    (deCODE genetics/Amgen Inc.)

  • Anna Bjornsdottir

    (Heilsuklasinn Clinic)

  • Olafur A. Sveinsson

    (University of Iceland)

  • Arnor Vikingsson

    (Landspitali—the National University Hospital of Iceland)

  • Thomas Folkmann Hansen

    (Copenhagen University Hospital, Rigshospitalet—Glostrup
    University of Copenhagen)

  • Rikke Louise Jacobsen

    (Copenhagen University Hospital—Rigshospitalet)

  • Christian Erikstrup

    (Aarhus University Hospital)

  • Michael Schwinn

    (Copenhagen University Hospital—Rigshospitalet)

  • Søren Brunak

    (University of Copenhagen)

  • Karina Banasik

    (University of Copenhagen)

  • Sisse Rye Ostrowski

    (Copenhagen University Hospital—Rigshospitalet
    University of Copenhagen)

  • Anders Troelsen

    (Copenhagen University Hospital)

  • Cecilie Henkel

    (Copenhagen University Hospital)

  • Ole Birger Pedersen

    (Zealand University Hospital—Køge)

  • Ingileif Jonsdottir

    (deCODE genetics/Amgen Inc.
    University of Iceland)

  • Daniel F. Gudbjartsson

    (deCODE genetics/Amgen Inc.
    University of Iceland)

  • Patrick Sulem

    (deCODE genetics/Amgen Inc.)

  • Thorgeir E. Thorgeirsson

    (deCODE genetics/Amgen Inc.)

  • Hreinn Stefansson

    (deCODE genetics/Amgen Inc.)

  • Kari Stefansson

    (deCODE genetics/Amgen Inc.
    University of Iceland)

Abstract

Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy and has a largely unknown underlying biology. In a genome-wide association study of CTS (48,843 cases and 1,190,837 controls), we found 53 sequence variants at 50 loci associated with the syndrome. The most significant association is with a missense variant (p.Glu366Lys) in SERPINA1 that protects against CTS (P = 2.9 × 10−24, OR = 0.76). Through various functional analyses, we conclude that at least 22 genes mediate CTS risk and highlight the role of 19 CTS variants in the biology of the extracellular matrix. We show that the genetic component to the risk is higher in bilateral/recurrent/persistent cases than nonrecurrent/nonpersistent cases. Anthropometric traits including height and BMI are genetically correlated with CTS, in addition to early hormonal-replacement therapy, osteoarthritis, and restlessness. Our findings suggest that the components of the extracellular matrix play a key role in the pathogenesis of CTS.

Suggested Citation

  • Astros Th. Skuladottir & Gyda Bjornsdottir & Egil Ferkingstad & Gudmundur Einarsson & Lilja Stefansdottir & Muhammad Sulaman Nawaz & Asmundur Oddsson & Thorunn A. Olafsdottir & Saedis Saevarsdottir & , 2022. "A genome-wide meta-analysis identifies 50 genetic loci associated with carpal tunnel syndrome," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29133-7
    DOI: 10.1038/s41467-022-29133-7
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    References listed on IDEAS

    as
    1. Saedis Saevarsdottir & Thorunn A. Olafsdottir & Erna V. Ivarsdottir & Gisli H. Halldorsson & Kristbjorg Gunnarsdottir & Asgeir Sigurdsson & Ari Johannesson & Jon K. Sigurdsson & Thorhildur Juliusdotti, 2020. "FLT3 stop mutation increases FLT3 ligand level and risk of autoimmune thyroid disease," Nature, Nature, vol. 584(7822), pages 619-623, August.
    2. Viechtbauer, Wolfgang, 2010. "Conducting Meta-Analyses in R with the metafor Package," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 36(i03).
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