RESEARCH PAPER
 
+ Co-first authors
KEYWORDS
TOPICS
ABSTRACT
Introduction:
It is currently uncertain whether smoking is a risk factor for carpal tunnel syndrome (CTS). This study aims to elucidate association between smoking and CTS using Mendelian randomization (MR) analysis.

Methods:
This study was a secondary analysis of publicly available GWAS data, using four smoking phenotypes (smoking initiation, smoking status, lifetime smoking, and never smoking) as exposures, and two CTS datasets (discovery and validation sets) as outcomes for MR analysis. The discovery set (n=480201) was used to explore the causal relationship between smoking and CTS, while the validation set (n=385304) was used to confirm the results. The effects of smoking on CTS were assessed using inverse variance weighted (IVW), MR-Egger, and weighted median methods. Cochran’s Q test was used to detect heterogeneity, and MREgger to test for pleiotropy. Finally, a meta-analysis was performed on the IVW results from both the discovery and validation sets.

Results:
IVW results showed that in both the discovery and validation sets, smoking initiation, smoking status, and lifetime smoking are risk factors for CTS. The summary results from the meta-analysis are as follows: smoking initiation (OR=1.17; 95% CI: 1.08–1.27, p<0.001), smoking status (OR=1.87; 95% CI: 1.56– 2.24, p<0.001), and lifetime smoking (OR=2.46; 95% CI: 2.03–3.00, p<0.001). Conversely, never smoking is a protective factor against CTS, with the summary result of the meta-analysis being: OR=0.55; 95% CI: 0.42–0.71, p<0.001.

Conclusions:
Based on genetic evidence, smoking may be a risk factor for CTS. Further clinical trials are needed to confirm this causal relationship.
ABBREVIATIONS
CTS: carpal tunnel syndrome, GWAS: genome-wide association study, IVW: inverse variance weighted, WM: weighted median, SNP: single nucleotide polymorphism, MR: Mendelian randomization
ACKNOWLEDGEMENTS
We extend our gratitude to the researchers who have shared their GWAS data, making this study possible, and to the FinnGen database for their support and contribution.
CONFLICTS OF INTEREST
The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none was reported.
FUNDING
This work was supported from the Natural Science Foundation of Tianjin (No. 23JCYBJC00700).
ETHICAL APPROVAL AND INFORMED CONSENT
Ethical approval and informed consent were not required for this study which was a secondary analysis of existing data.
DATA AVAILABILITY
The data supporting this research are available from the following sources: The GWAS data for Smoking initiation, Smoking status, Never smoked, and CTS (discovery set) can be downloaded from the IEU database https://gwas.mrcieu.ac.uk/datasets/ with the registration numbers ieu-b-4877, ebi-a-GCST90029014, ukb-d-20116_0, ebi-a- GCST90018813. Lifetime smoking GWAS summary data are available for download at https://doi.org/10.5523/bris.10i96zb8gm0j81yz0q6ztei23d CTS (validation) data in the FinnGen database download: https:// storage.googleapis.com/finngen-public-data-r10/summary_stats/ finngen_R10_G6_CARPTU.gz
AUTHORS' CONTRIBUTIONS
WS: data curation, writing of the original draft. KW: visualization. HZ and HL: writing, editing and reviewing of the manuscript. All authors read and approved the final version of the manuscript.
PROVENANCE AND PEER REVIEW
Not commissioned; externally peer reviewed.
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