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Nat Commun. 2019 Mar 4;10(1):1030. doi: 10.1038/s41467-019-08993-6.

A genome-wide association analysis identifies 16 novel susceptibility loci for carpal tunnel syndrome.

Author information

1
Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Science, University of Oxford, Botnar Research Centre, Windmill Road, Oxford, OX3 7LD, UK.
2
Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
3
Department of Plastic and Reconstructive Surgery, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
4
Medical Research Council Population Health Research Unit at the University of Oxford, Oxford, OX3 7LF, UK.
5
Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Richard Doll Building, Old Road Campus, Roosevelt Drive, Oxford, OX3 7LF, UK.
6
Institute of Technology, University of Tartu, Nooruse 1, 50411, Tartu, Estonia.
7
Estonian Genome Center, Institute of Genomics, University of Tartu, Riia 23 B, 51010, Tartu, Estonia.
8
Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, UK. david.bennett@ndcn.ox.ac.uk.
9
Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Science, University of Oxford, Botnar Research Centre, Windmill Road, Oxford, OX3 7LD, UK. dominic.furniss@ndorms.ox.ac.uk.
10
Department of Plastic and Reconstructive Surgery, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, OX3 9DU, UK. dominic.furniss@ndorms.ox.ac.uk.

Abstract

Carpal tunnel syndrome (CTS) is a common and disabling condition of the hand caused by entrapment of the median nerve at the level of the wrist. It is the commonest entrapment neuropathy, with estimates of prevalence ranging between 5-10%. Here, we undertake a genome-wide association study (GWAS) of an entrapment neuropathy, using 12,312 CTS cases and 389,344 controls identified in UK Biobank. We discover 16 susceptibility loci for CTS with p < 5 × 10-8. We identify likely causal genes in the pathogenesis of CTS, including ADAMTS17, ADAMTS10 and EFEMP1, and using RNA sequencing demonstrate expression of these genes in surgically resected tenosynovium from CTS patients. We perform Mendelian randomisation and demonstrate a causal relationship between short stature and higher risk of CTS. We suggest that variants within genes implicated in growth and extracellular matrix architecture contribute to the genetic predisposition to CTS by altering the environment through which the median nerve transits.

PMID:
30833571
PMCID:
PMC6399342
DOI:
10.1038/s41467-019-08993-6
[Indexed for MEDLINE]
Free PMC Article

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