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

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


Title: A genome-wide meta-analysis identifies 50 genetic loci associated with carpal tunnel syndrome
Author: DBDS Genetic Consortium
Date: 2022-03-24
Language: English
Scope: 1715148
University/Institute: Landspitali - The National University Hospital of Iceland
Department: Faculty of Medicine
Series: Nature Communications; 13(1)
ISSN: 2041-1723
DOI: 10.1038/s41467-022-29133-7
Subject: Gigtarlæknisfræði; Anthropometry; Carpal Tunnel Syndrome/genetics; Genetic Loci; Genome-Wide Association Study; Humans; Phenotype; Multidisciplinary; Physics and Astronomy (all); Chemistry (all); Biochemistry, Genetics and Molecular Biology (all)
URI: https://hdl.handle.net/20.500.11815/3193

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Citation:

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

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.

Description:

Funding Information: We thank the participants in this study for their valuable contribution to the research. We thank all investigators and colleagues who contributed to data collection, phenotypic characterization of clinical samples, genotyping, and analysis of the whole-genome association data. This research was conducted using the UK Biobank Resource (application number 24898). We acknowledge the participants and investigators of the FinnGen study. The financial support from the European Commission to the painFACT project, TET, (H2020-2020-848099) is acknowledged. Publisher Copyright: © 2022, The Author(s).

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