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

Astros Th Skuladottir*, Gyda Bjornsdottir, Egil Ferkingstad, Gudmundur Einarsson, Lilja Stefansdottir, Muhammad Sulaman Nawaz, Asmundur Oddsson, Thorunn A Olafsdottir, Saedis Saevarsdottir, G Bragi Walters, Sigurdur H Magnusson, Anna Bjornsdottir, Olafur A Sveinsson, Arnor Vikingsson, Thomas Folkmann Hansen, Rikke Louise Jacobsen, Christian Erikstrup, Michael Schwinn, Søren Brunak, Karina BanasikSisse Rye Ostrowski, Anders Troelsen, Cecilie Henkel, Ole Birger Pedersen, Ingileif Jonsdottir, Daniel F Gudbjartsson, Patrick Sulem, Thorgeir E Thorgeirsson, Hreinn Stefansson, Kari Stefansson, DBDS Genetic Consortium, Poul Jørgen Jennum (Member of study group), Kristoffer Sølvsten Burgdorf (Member of study group)

*Corresponding author for this work
7 Citations (Scopus)


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
Issue number1
Pages (from-to)1-9
Number of pages9
Publication statusPublished - 24 Mar 2022


  • Anthropometry
  • Carpal Tunnel Syndrome/genetics
  • Genetic Loci
  • Genome-Wide Association Study
  • Humans
  • Phenotype


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