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

Authors :
Skuladottir, Astros Th.
Bjornsdottir, Gyda
Ferkingstad, Egil
Einarsson, Gudmundur
Stefansdottir, Lilja
Nawaz, Muhammad Sulaman
Oddsson, Asmundur
Olafsdottir, Thorunn A.
Saevarsdottir, Saedis
Walters, G. Bragi
Magnusson, Sigurdur H.
Bjornsdottir, Anna
Sveinsson, Olafur A.
Vikingsson, Arnor
Hansen, Thomas Folkmann
Jacobsen, Rikke Louise
Erikstrup, Christian
Schwinn, Michael
Brunak, Søren
Banasik, Karina
Ostrowski, Sisse Rye
Troelsen, Anders
Henkel, Cecilie
Pedersen, Ole Birger
Andersen, Steffen
Burgdorf, Kristoffer
Didriksen, Maria
Dinh, Khoa Manh
Hjalgrim, Henrik
Jemec, Gregor
Jennum, Poul
Johansson, Pär Ingemar
Larsen, Margit Anita Hørup
Mikkelsen, Susan
Nielsen, Kasper Rene
Nyegaard, Mette
Stefánsson, Hreinn
Sækmose, Susanne
Sørensen, Erik
Thorsteinsdottir, Unnur
Bruun, Mie Topholm
Ullum, Henrik
Werge, Thomas
Jonsdottir, Ingileif
Gudbjartsson, Daniel F.
Sulem, Patrick
Thorgeirsson, Thorgeir E.
Stefansson, Hreinn
Stefansson, Kari
Source :
Skuladottir, A T, Bjornsdottir, G, Ferkingstad, E, Einarsson, G, Stefansdottir, L, Nawaz, M S, Oddsson, A, Olafsdottir, T A, Saevarsdottir, S, Walters, G B, Magnusson, S H, Bjornsdottir, A, Sveinsson, O A, Vikingsson, A, Hansen, T F, Jacobsen, R L, Erikstrup, C, Schwinn, M, Brunak, S, Banasik, K, Ostrowski, S R, Troelsen, A, Henkel, C, Pedersen, O B, DBDS Genetic Consortium, Jonsdottir, I, Gudbjartsson, D F, Sulem, P, Thorgeirsson, T E, Stefansson, H & Stefansson, K 2022, ' A genome-wide meta-analysis identifies 50 genetic loci associated with carpal tunnel syndrome ', Nature Communications, vol. 13, 1598 . https://doi.org/10.1038/s41467-022-29133-7, Skuladottir, A T, Bjornsdottir, G, Ferkingstad, E, Einarsson, G, Stefansdottir, L, Nawaz, M S, Oddsson, A, Olafsdottir, T A, Saevarsdottir, S, Walters, G B, Magnusson, S H, Bjornsdottir, A, Sveinsson, O A, Vikingsson, A, Hansen, T F, Jacobsen, R L, Erikstrup, C, Schwinn, M, Brunak, S, Banasik, K, Ostrowski, S R, Troelsen, A, Henkel, C, Pedersen, O B, Jonsdottir, I, Gudbjartsson, D F, Sulem, P, Thorgeirsson, T E, Stefansson, H, Stefansson, K, DBDS Genetic Consortium, Nyegaard, M & Nielsen, K R 2022, ' A genome-wide meta-analysis identifies 50 genetic loci associated with carpal tunnel syndrome ', Nature Communications, vol. 13, no. 1, 1598 . https://doi.org/10.1038/s41467-022-29133-7, Skuladottir, A T, Bjornsdottir, G, Ferkingstad, E, Einarsson, G, Stefansdottir, L, Nawaz, M S, Oddsson, A, Olafsdottir, T A, Saevarsdottir, S, Walters, G B, Magnusson, S H, Bjornsdottir, A, Sveinsson, O A, Vikingsson, A, Hansen, T F, Jacobsen, R L, Erikstrup, C, Schwinn, M, Brunak, S, Banasik, K, Ostrowski, S R, Troelsen, A, Henkel, C, Pedersen, O B, Jonsdottir, I, Gudbjartsson, D F, Sulem, P, Thorgeirsson, T E, Stefansson, H, Stefansson, K & DBDS Genetic Consortium 2022, ' A genome-wide meta-analysis identifies 50 genetic loci associated with carpal tunnel syndrome ', Nature Communications, vol. 13, no. 1, 1598 . https://doi.org/10.1038/s41467-022-29133-7, Nature Communications, Skuladottir, A T, Bjornsdottir, G, Ferkingstad, E, Einarsson, G, Stefansdottir, L, Nawaz, M S, Oddsson, A, Olafsdottir, T A, Saevarsdottir, S, Walters, G B, Magnusson, S H, Bjornsdottir, A, Sveinsson, O A, Vikingsson, A, Hansen, T F, Jacobsen, R L, Erikstrup, C, Schwinn, M, Brunak, S, Banasik, K, Ostrowski, S R, Troelsen, A, Henkel, C, Pedersen, O B, Jonsdottir, I, Gudbjartsson, D F, Sulem, P, Thorgeirsson, T E, Stefansson, H, Stefansson, K, DBDS Genetic Consortium & Bruun, M T 2022, ' A genome-wide meta-analysis identifies 50 genetic loci associated with carpal tunnel syndrome ', Nature Communications, vol. 13, no. 1, 1598 . https://doi.org/10.1038/s41467-022-29133-7
Publication Year :
2022

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.

Details

Language :
English
Database :
OpenAIRE
Journal :
Skuladottir, A T, Bjornsdottir, G, Ferkingstad, E, Einarsson, G, Stefansdottir, L, Nawaz, M S, Oddsson, A, Olafsdottir, T A, Saevarsdottir, S, Walters, G B, Magnusson, S H, Bjornsdottir, A, Sveinsson, O A, Vikingsson, A, Hansen, T F, Jacobsen, R L, Erikstrup, C, Schwinn, M, Brunak, S, Banasik, K, Ostrowski, S R, Troelsen, A, Henkel, C, Pedersen, O B, DBDS Genetic Consortium, Jonsdottir, I, Gudbjartsson, D F, Sulem, P, Thorgeirsson, T E, Stefansson, H & Stefansson, K 2022, ' A genome-wide meta-analysis identifies 50 genetic loci associated with carpal tunnel syndrome ', Nature Communications, vol. 13, 1598 . https://doi.org/10.1038/s41467-022-29133-7, Skuladottir, A T, Bjornsdottir, G, Ferkingstad, E, Einarsson, G, Stefansdottir, L, Nawaz, M S, Oddsson, A, Olafsdottir, T A, Saevarsdottir, S, Walters, G B, Magnusson, S H, Bjornsdottir, A, Sveinsson, O A, Vikingsson, A, Hansen, T F, Jacobsen, R L, Erikstrup, C, Schwinn, M, Brunak, S, Banasik, K, Ostrowski, S R, Troelsen, A, Henkel, C, Pedersen, O B, Jonsdottir, I, Gudbjartsson, D F, Sulem, P, Thorgeirsson, T E, Stefansson, H, Stefansson, K, DBDS Genetic Consortium, Nyegaard, M & Nielsen, K R 2022, ' A genome-wide meta-analysis identifies 50 genetic loci associated with carpal tunnel syndrome ', Nature Communications, vol. 13, no. 1, 1598 . https://doi.org/10.1038/s41467-022-29133-7, Skuladottir, A T, Bjornsdottir, G, Ferkingstad, E, Einarsson, G, Stefansdottir, L, Nawaz, M S, Oddsson, A, Olafsdottir, T A, Saevarsdottir, S, Walters, G B, Magnusson, S H, Bjornsdottir, A, Sveinsson, O A, Vikingsson, A, Hansen, T F, Jacobsen, R L, Erikstrup, C, Schwinn, M, Brunak, S, Banasik, K, Ostrowski, S R, Troelsen, A, Henkel, C, Pedersen, O B, Jonsdottir, I, Gudbjartsson, D F, Sulem, P, Thorgeirsson, T E, Stefansson, H, Stefansson, K & DBDS Genetic Consortium 2022, ' A genome-wide meta-analysis identifies 50 genetic loci associated with carpal tunnel syndrome ', Nature Communications, vol. 13, no. 1, 1598 . https://doi.org/10.1038/s41467-022-29133-7, Nature Communications, Skuladottir, A T, Bjornsdottir, G, Ferkingstad, E, Einarsson, G, Stefansdottir, L, Nawaz, M S, Oddsson, A, Olafsdottir, T A, Saevarsdottir, S, Walters, G B, Magnusson, S H, Bjornsdottir, A, Sveinsson, O A, Vikingsson, A, Hansen, T F, Jacobsen, R L, Erikstrup, C, Schwinn, M, Brunak, S, Banasik, K, Ostrowski, S R, Troelsen, A, Henkel, C, Pedersen, O B, Jonsdottir, I, Gudbjartsson, D F, Sulem, P, Thorgeirsson, T E, Stefansson, H, Stefansson, K, DBDS Genetic Consortium & Bruun, M T 2022, ' A genome-wide meta-analysis identifies 50 genetic loci associated with carpal tunnel syndrome ', Nature Communications, vol. 13, no. 1, 1598 . https://doi.org/10.1038/s41467-022-29133-7
Accession number :
edsair.doi.dedup.....f0e1fb461e6039948999410e47252af3
Full Text :
https://doi.org/10.1038/s41467-022-29133-7