AbstractBackgroundWe aimed to examine evidence for a causal effect of overall and abdominal adiposity on carpal tunnel syndrome (CTS) using two-sample Mendelian randomization (MR).MethodsThe exposure included genetic instruments comprising independent variants associated with body mass index (BMI) (n=322,154), a proxy for overall adiposity, and waist-hip ratio adjusted for BMI (WHRadjBMI) (n=210,082), a proxy for abdominal adiposity. Associations of these variants with CTS were obtained from a genome-wide association study (GWAS) conducted in UK Biobank (12,312 CTS cases / 389,344 controls). Causal effects were estimated using inverse-variance weighted regression and conventional MR sensitivity analyses were conducted to assess for horizontal pleiotropy. In follow-up analyses we determined whether type 2 diabetes (T2D) or hyperlipidemia mediated the observed effects.ResultsA 1-standard deviation (SD, ∼4.7kg/m2) increase in genetically instrumented BMI increased the risk of CTS (OR 1.73, 95% CI 1.48-2.02, p=2.68e-12), with consistent effects across sensitivity analyses. This effect translates to an absolute increase of 17 CTS cases per 1000 person years amongst US working populations [95% CI 11.0-23.5]. Univariable MR was consistent with a causal effect of T2D (OR 1.08, 95% CI 1.03-1.11, p=5.20e-05), and the effect of BMI was partially attenuated (OR 1.53, 95% CI 1.38-1.68, p=2.85e-08) when controlling for T2D liability in multivariable MR. In contrast, no effect was observed of WHRadjBMI on CTS (OR 1.03, 95% CI 0.74-1.33, p=0.83).ConclusionThese data support a causal effect of overall adiposity on susceptibility to CTS that is only partially mediated through T2D, suggesting that efforts to reduce obesity may mitigate the population burden of CTS.Key messages- A one-standard deviation increase in body mass index, a proxy for overall adiposity, increased risk of carpal tunnel by 73%. In contrast, no effect of waist-to-hip ratio adjusted for BMI, a proxy for abdominal adiposity, was observed on risk of carpal tunnel syndrome.- The effects of BMI on carpal tunnel syndrome risk were partially attenuated when accounting for mediation through type 2 diabetes, suggesting that the majority of the causal effect operates independently of diabetes risk.- These data suggest that efforts to reduce rates of obesity could reduce the incidence of carpal tunnel syndrome.
Case Report: Presentation of an unusual cause of carpal tunnel syndrome with accompanying literature review
