Abstract
Some previous observational studies have reported an increased risk of carpal tunnel syndrome (CTS) in patients with obesity or type 2 diabetes (T2D), which was however, not observed in some other studies. In this study we performed a two-sample Mendelian randomization to assess the causal effect of obesity, T2D on the risk of CTS. Single nucleotide polymorphisms associated with the body mass index (BMI) and T2D were extracted from genome-wide association studies. Summary-level results of CTS were available through FinnGen repository. Univariable Mendelian randomization (MR) with inverse-variance-weighted method indicated a positive correlation of BMI with CTS risk [odds ratio (OR) 1.66, 95% confidence interval (CI), 1.39–1.97]. Genetically proxied T2D also significantly increased the risk of CTS [OR 1.17, 95% CI (1.07–1.29)]. The causal effect of BMI and T2D on CTS remained consistent after adjusting for each other with multivariable MR. Our mediation analysis indicated that 34.4% of BMI’s effect of CTS was mediated by T2D. We also assessed the effects of several BMI and glycemic related traits on CTS. Waist circumference and arm fat-free mass were also causally associated with CTS. However, the associations disappeared after adjusting for the effect of BMI. Our findings indicate that obesity and T2D are independent risk factors of CTS.
Highlights
Carpal tunnel syndrome (CTS) is an entrapment neuropathy caused by the compression of the median nerve in the carpal tunnel of the waist
For 1-SD increase in body mass index (BMI) level, the odds ratios (ORs) of carpal tunnel syndrome (CTS) were 1.66 [95% confidence interval (CI), 1.39–1.97, p = 1.36 × 10−8] with IVW method, 2.08 with weighted median method
After adjusting for type 2 diabetes (T2D), BMI was still causally associated with an increased risk of CTS, with an OR of 1.62
Summary
Carpal tunnel syndrome (CTS) is an entrapment neuropathy caused by the compression of the median nerve in the carpal tunnel of the waist. Despite the high incidence rate of CTS, the cause of most CTS cases is unknown (Atroshi et al, 1999; Sternbach, 1999). The relationships still remain controversial, as the observations are not consistent in other studies (Frost et al, 1998; Shiri et al, 2011). These findings mainly come from cross-sectional studies or cohort studies, which may be affected by confounding factors or reverse causality
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