Smoking may be a risk factor for carpal tunnel syndrome: Insights from Mendelian randomization analysis

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.

Keywords

• carpal tunnel syndrome
• gwas
• pain
• risk factor
• smoking