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

Ástrós Skúladóttir(deCODE Genetics (Iceland)), Gyða Björnsdóttir(deCODE Genetics (Iceland)), Egil Ferkingstad(deCODE Genetics (Iceland)), Guðmundur Einarsson(deCODE Genetics (Iceland)), Lilja Stefánsdóttir(deCODE Genetics (Iceland)), Muhammad Sulaman Nawaz(deCODE Genetics (Iceland)), Ásmundur Oddsson(deCODE Genetics (Iceland)), Thorunn A. Olafsdottir(deCODE Genetics (Iceland)), Saedís Saevarsdóttir(deCODE Genetics (Iceland)), G. Bragi Walters(deCODE Genetics (Iceland)), Sigurður H. Magnússon(deCODE Genetics (Iceland)), Anna Bjornsdottir, Ólafur Sveinsson(University of Iceland), Arnór Víkingsson(National University Hospital of Iceland), Thomas Folkmann Hansen(University of Copenhagen), Rikke Louise Jacobsen(Copenhagen University Hospital), Christian Erikstrup(Aarhus University Hospital), Michael Schwinn(Copenhagen University Hospital), Søren Brunak(University of Copenhagen), Karina Banasik(University of Copenhagen), Sisse Rye Ostrowski(University of Copenhagen), Anders Troelsen(Copenhagen University Hospital), Cecilie Henkel(Copenhagen University Hospital), Ole Birger Pedersen(Zealand University Hospital), Steffen Andersen(Copenhagen Business School), Kristoffer Sølvsten Burgdorf(Copenhagen University Hospital), Maria Didriksen(Copenhagen University Hospital), Khoa Manh Dinh(Aarhus University Hospital), Henrik Hjalgrim(Statens Serum Institut), Gregor B. E. Jemec(Zealand University Hospital), Poul Jennum(University of Copenhagen), Pär I. Johansson(Copenhagen University Hospital), Margit Anita Hørup Larsen(Copenhagen University Hospital), Susan Mikkelsen(Aarhus University Hospital), Kasper Nielsen(Aalborg University Hospital), Mette Nyegaard(Aarhus University), Hreinn Stefánsson(deCODE Genetics (Iceland)), Susanne Gjørup Sækmose(Zealand University Hospital Køge), Erik Sørensen(Copenhagen University Hospital), Unnur Þorsteinsdóttir(deCODE Genetics (Iceland)), Mie Topholm Bruun(Odense University Hospital), Henrik Ullum(Statens Serum Institut), Thomas Werge(Sankt Hans Hospital), Ingileif Jónsdóttir(deCODE Genetics (Iceland)), Daníel F. Guðbjartsson(deCODE Genetics (Iceland)), Patrick Sulem(deCODE Genetics (Iceland)), Thorgeir E. Thorgeirsson(deCODE Genetics (Iceland)), Hreinn Stefánsson(deCODE Genetics (Iceland)), Kāri Stefánsson(deCODE Genetics (Iceland))
Nature Communications
March 24, 2022
10.1038/s41467-022-29133-7
Cited by 35Open Access
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Abstract

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.

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