RESEARCH PAPER
Smoking may be a risk factor for carpal tunnel syndrome: Insights from Mendelian randomization analysis
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1
Department of Orthopedics,
Tianjin Medical University
General Hospital, Tianjin,
People’s Republic of China
2
Department of
Orthopedics, Tianjin University Central
Hospital, Tianjin, People’s
Republic of China
These authors had equal contribution to this work
Submission date: 2024-09-03
Final revision date: 2025-01-07
Acceptance date: 2025-01-10
Publication date: 2025-01-30
Corresponding author
Huafeng Zhang
Tianjin Medical University General Hospital, No. 22,
Qixiangtai Rd, Heping Dist.,
Tianjin 300052, People’s
Republic of China
Tob. Induc. Dis. 2025;23(January):9
+ 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
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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