scholarly journals A genome-wide meta-analysis identifies 53 sequence variants associating with carpal tunnel syndrome

Astros Skuladottir ◽  
Gyda Bjornsdottir ◽  
Egil Ferkingstad ◽  
Gudmundur Einarsson ◽  
Lilja Stefansdottir ◽  

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 (Ncases = 48,843, Ncontrols = 1,190,837), we found 53 sequence variants at 50 loci that associate 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 recurrent/persistent cases than nonrecurrent/nonresistant 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.

2021 ◽  
Benjamin Patel ◽  
Sam O. Kleeman ◽  
Drew Neavin ◽  
Joseph Powell ◽  
Georgios Baskozos ◽  

AbstractTrigger finger (TF) and carpal tunnel syndrome (CTS) are two common non-traumatic hand disorders that frequently co-occur. By identifying TF and CTS cases in UK Biobank (UKB), we confirmed a highly significant phenotypic association between the diseases. To investigate the genetic basis for this association we performed a genome-wide association study (GWAS) including 2,908 TF cases and 436,579 European controls in UKB, identifying five independent loci. Colocalization with CTS summary statistics identified a co-localized locus at DIRC3 (lncRNA), which was replicated in FinnGen and fine-mapped to rs62175241. Single-cell and bulk eQTL analysis in fibroblasts from healthy donors (n=79) and tenosynovium samples from CTS patients (n=77) showed that the disease-protective rs62175241 allele was associated with increased DIRC3 and IGFBP5 expression. IGFBP5 is a secreted antagonist of IGF-1 signaling, and elevated IGF-1 levels were associated with CTS and TF in UKB, thereby implicating IGF-1 as a driver of both diseases.

2021 ◽  
Vol 4 (1) ◽  
Astros Th. Skuladottir ◽  
Gyda Bjornsdottir ◽  
Muhammad Sulaman Nawaz ◽  
Hannes Petersen ◽  
Solvi Rognvaldsson ◽  

AbstractVertigo is the leading symptom of vestibular disorders and a major risk factor for falls. In a genome-wide association study of vertigo (Ncases = 48,072, Ncontrols = 894,541), we uncovered an association with six common sequence variants in individuals of European ancestry, including missense variants in ZNF91, OTOG, OTOGL, and TECTA, and a cis-eQTL for ARMC9. The association of variants in ZNF91, OTOGL, and OTOP1 was driven by an association with benign paroxysmal positional vertigo. Using previous reports of sequence variants associating with age-related hearing impairment and motion sickness, we found eight additional variants that associate with vertigo. Although disorders of the auditory and the vestibular system may co-occur, none of the six genome-wide significant vertigo variants were associated with hearing loss and only one was associated with age-related hearing impairment. Our results uncovered sequence variants associating with vertigo in a genome-wide association study and implicated genes with known roles in inner ear development, maintenance, and disease.

2021 ◽  
pp. 175319342110017
Saskia F. de Roo ◽  
Philippe N. Sprangers ◽  
Erik T. Walbeehm ◽  
Brigitte van der Heijden

We performed a systematic review on the success of different surgical techniques for the management of recurrent and persistent carpal tunnel syndrome. Twenty studies met the inclusion criteria and were grouped by the type of revision carpal tunnel release, which were simple open release, open release with flap coverage or open release with implant coverage. Meta-analysis showed no difference, and pooled success proportions were 0.89, 0.89 and 0.85 for simple open carpal tunnel release, additional flap coverage and implant groups, respectively. No added value for coverage of the nerve was seen. Our review indicates that simple carpal tunnel release without additional coverage of the median nerve seems preferable as it is less invasive and without additional donor site morbidity. We found that the included studies were of low quality with moderate risk of bias and did not differentiate between persistent and recurrent carpal tunnel syndrome.

2013 ◽  
Vol 49 (3) ◽  
pp. 345-350 ◽  
Mohammad-Hossein Pourmemari ◽  
Eira Viikari-Juntura ◽  
Rahman Shiri

Ahmed M. Ahmed ◽  
Osama G. Hassan ◽  
Ahmed A. Khalifa

Abstract Background Carpal tunnel syndrome (CTS) is a common upper limb entrapment neuropathy; severe cases are treated surgically and mild to moderate can be managed conservatively. The purpose of this systematic review and meta-analysis was to define the efficacy of gabapentin as an adjuvant to splinting in the treatment of mild to moderate CTS. Methods A systematic search through 13 databases, randomized clinical trials (RCTs) reporting the use of gabapentin with splinting in CTS were included and analyzed. Results Three RCTs including 170 patients were eligible. There was no significant difference between gabapentin plus splinting and splinting alone in 5 measured parameters: (1) Symptom Severity Scale (SSS) [MD (95% CI) = − 0.76 (− 2.46–0.93), p = 0.378], (2) Functional Status Scale (FSS) [MD (95% CI) = − 0.23 (− 1.40–0.94), p = 0.701], (3) visual analogue scale (VAS) to assess pain [MD (95% CI) = − 0.6 (− 1.47–0.27), p = 0.174], (4) Grip strength [MD (95% CI) = − 0.11 (− 0.70–0.48), p = 0.718], and (5) pinch strength [MD (95% CI) = 0.72 (− 0.10–1.54), p = 0.083]. Conclusion This review provides low-quality evidence that gabapentin plus nocturnal splinting is not superior to splinting alone. More high-quality trials are needed to determine the role of this drug as an adjuvant in the management of CTS.

2021 ◽  
Vol 108 (Supplement_6) ◽  
F La Costa

Abstract Introduction Carpal tunnel syndrome (CTS) is caused by compression of the median nerve at the wrist. It accounts for 90% of all entrapment neuropathies, with a 7-16% in the UK. It has a significant impact on patients’ daily lives. Clinically, CTS results in paraesthesia, while extreme cases may involve muscular atrophy and weakness. There is currently a disparity between optimal treatments for CTS. Therefore, this paper aims to identify the optimal treatment for CTS with post-treatment BCTQ (Boston Carpal Tunnel Questionnaire) scores (including both functional and symptomatic severity) at 1, 3 and 6 months. Method The BCTQ scores for were sited from PubMed, Google Scholar and the University of Dundee Library search engine by entering key words such as “carpal tunnel syndrome”, “surgical decompression”, “surgical release” and “steroid injection”. Means and standard deviations for pre- and post-treatment after 1, 3 and 6 months were obtained. From this, forest plots were constructed using a software where steroid injection and surgical decompression were inputted separately, and effect sizes were then compared for 1, 3 and 6 months. Results The meta-analysis included reviewing 133 articles. The effect size was determined using the random effects model. Steroid injection was more effective than surgical decompression after 1 and 3 months. However, after 6 months, surgical decompression was more effective. Conclusions Identification of long-term relief of CTS through surgical decompression allows the reduction of symptom recurrence and thus costly follow-up appointments. This study provides robust clinical findings for the optimal treatment of CTS.

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