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

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Astros Th Skuladottir, deCODE Genetics
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  • Gyda Bjornsdottir, deCODE Genetics
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  • Egil Ferkingstad, deCODE Genetics
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  • Gudmundur Einarsson, deCODE Genetics
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  • Lilja Stefansdottir, deCODE Genetics
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  • Muhammad Sulaman Nawaz, deCODE Genetics, University of Iceland
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  • Asmundur Oddsson, deCODE Genetics
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  • Thorunn A. Olafsdottir, deCODE Genetics
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  • Saedis Saevarsdottir, deCODE Genetics, University of Iceland, Landspitali University Hospital
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  • G. Bragi Walters, deCODE Genetics, University of Iceland
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  • Sigurdur H. Magnusson, deCODE Genetics
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  • Anna Bjornsdottir, Heilsuklasinn Clinic
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  • Olafur A. Sveinsson, University of Iceland
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  • Arnor Vikingsson, Landspitali University Hospital
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  • Thomas Folkmann Hansen, University of Copenhagen
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  • Rikke Louise Jacobsen, University of Copenhagen
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  • Christian Erikstrup
  • Michael Schwinn, University of Copenhagen
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  • Søren Brunak, University of Copenhagen
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  • Karina Banasik, University of Copenhagen
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  • Sisse Rye Ostrowski, University of Copenhagen
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  • Anders Troelsen, University of Copenhagen
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  • Cecilie Henkel, University of Copenhagen
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  • Ole Birger Pedersen, Sjællands Universitetshospital
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  • DBDS Genetic Consortium
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  • Ingileif Jonsdottir, deCODE Genetics, University of Iceland
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  • Daniel F. Gudbjartsson, deCODE Genetics, University of Iceland
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  • Patrick Sulem, deCODE Genetics
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  • Thorgeir E. Thorgeirsson, deCODE Genetics
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  • Hreinn Stefansson, deCODE Genetics
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  • Kari Stefansson, deCODE Genetics, University of Iceland

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.

Original languageEnglish
Article number1598
JournalNature Communications
Volume13
ISSN2041-1723
DOIs
Publication statusPublished - Mar 2022

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