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 Banasik; Sisse 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; Mette Nyegaard; Kaspar René Nielsen

doi:10.1038/s41467-022-29133-7

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, Mette Nyegaard (Member of study group), Kaspar René Nielsen (Member of study group)

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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.

Original language	English
Article number	1598
Journal	Nature Communications
Volume	13
Issue number	1
Number of pages	9
ISSN	2041-1723
DOIs	https://doi.org/10.1038/s41467-022-29133-7
Publication status	Published - 24 Mar 2022

Bibliographical note

Keywords

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

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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., ... Nielsen, K. R. (2022). A genome-wide meta-analysis identifies 50 genetic loci associated with carpal tunnel syndrome. Nature Communications, 13(1), Article 1598. https://doi.org/10.1038/s41467-022-29133-7

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title = "A genome-wide meta-analysis identifies 50 genetic loci associated with carpal tunnel syndrome",

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.",

keywords = "Anthropometry, Carpal Tunnel Syndrome/genetics, Genetic Loci, Genome-Wide Association Study, Humans, Phenotype",

author = "Skuladottir, {Astros Th} and Gyda Bjornsdottir and Egil Ferkingstad and Gudmundur Einarsson and Lilja Stefansdottir and Nawaz, {Muhammad Sulaman} and Asmundur Oddsson and Olafsdottir, {Thorunn A} and Saedis Saevarsdottir and Walters, {G Bragi} and Magnusson, {Sigurdur H} and Anna Bjornsdottir and Sveinsson, {Olafur A} and Arnor Vikingsson and Hansen, {Thomas Folkmann} and Jacobsen, {Rikke Louise} and Christian Erikstrup and Michael Schwinn and S{\o}ren Brunak and Karina Banasik and Ostrowski, {Sisse Rye} and Anders Troelsen and Cecilie Henkel and Pedersen, {Ole Birger} and Ingileif Jonsdottir and Gudbjartsson, {Daniel F} and Patrick Sulem and Thorgeirsson, {Thorgeir E} and Hreinn Stefansson and Kari Stefansson and {DBDS Genetic Consortium} and Mette Nyegaard and Nielsen, {Kaspar Ren{\'e}}",

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doi = "10.1038/s41467-022-29133-7",

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Skuladottir, AT, Bjornsdottir, G, Ferkingstad, E, Einarsson, G, Stefansdottir, L, Nawaz, MS, Oddsson, A, Olafsdottir, TA, Saevarsdottir, S, Walters, GB, Magnusson, SH, Bjornsdottir, A, Sveinsson, OA, Vikingsson, A, Hansen, TF, Jacobsen, RL, Erikstrup, C, Schwinn, M, Brunak, S, Banasik, K, Ostrowski, SR, Troelsen, A, Henkel, C, Pedersen, OB, Jonsdottir, I, Gudbjartsson, DF, Sulem, P, Thorgeirsson, TE, Stefansson, H, Stefansson, K, DBDS Genetic Consortium, Nyegaard, M & Nielsen, KR 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

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

A2 - Nyegaard, Mette

A2 - Nielsen, Kaspar René

PY - 2022/3/24

Y1 - 2022/3/24

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.

KW - Anthropometry

KW - Carpal Tunnel Syndrome/genetics

KW - Genetic Loci

KW - Genome-Wide Association Study

KW - Humans

KW - Phenotype

UR - http://www.scopus.com/inward/record.url?scp=85127057473&partnerID=8YFLogxK

U2 - 10.1038/s41467-022-29133-7

DO - 10.1038/s41467-022-29133-7

M3 - Journal article

C2 - 35332129

SN - 2041-1723

VL - 13

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 1598

ER -

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

Abstract

Bibliographical note

Keywords

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