TY - JOUR
T1 - A genome-wide meta-analysis identifies 50 genetic loci associated with carpal tunnel syndrome
AU - Skuladottir, Astros Th
AU - Bjornsdottir, Gyda
AU - Ferkingstad, Egil
AU - Einarsson, Gudmundur
AU - Stefansdottir, Lilja
AU - Nawaz, Muhammad Sulaman
AU - Oddsson, Asmundur
AU - Olafsdottir, Thorunn A.
AU - Saevarsdottir, Saedis
AU - Walters, G. Bragi
AU - Magnusson, Sigurdur H.
AU - Bjornsdottir, Anna
AU - Sveinsson, Olafur A.
AU - Vikingsson, Arnor
AU - Hansen, Thomas Folkmann
AU - Jacobsen, Rikke Louise
AU - Erikstrup, Christian
AU - Schwinn, Michael
AU - Brunak, Søren
AU - Banasik, Karina
AU - Ostrowski, Sisse Rye
AU - Troelsen, Anders
AU - Henkel, Cecilie
AU - Pedersen, Ole Birger
AU - Jonsdottir, Ingileif
AU - Gudbjartsson, Daniel F.
AU - Sulem, Patrick
AU - Thorgeirsson, Thorgeir E.
AU - Stefansson, Hreinn
AU - Stefansson, Kari
AU - DBDS Genetic Consortium
N1 - Publisher Copyright:
© 2022. The Author(s).
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-022-29133-7
DO - 10.1038/s41467-022-29133-7
M3 - Journal article
C2 - 35332129
AN - SCOPUS:85127057473
VL - 13
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 1598
ER -