Table_1_Obesity, Type 2 Diabetes, and the Risk of Carpal Tunnel Syndrome: A Two-Sample Mendelian Randomization Study.XLSX

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.

既往的观察性研究表明，肥胖或2型糖尿病（T2D）患者患腕管综合征（CTS）的风险增加，然而，在一些其他研究中并未观察到这种现象。在本研究中，我们执行了双样本孟德尔随机化分析，以评估肥胖、T2D对CTS风险的因果效应。从全基因组关联研究中提取了与体质指数（BMI）和T2D相关的单核苷酸多态性。CTS的汇总级别结果可通过FinnGen数据库获取。单变量孟德尔随机化（MR）采用逆方差加权法表明，BMI与CTS风险呈正相关[比值比（OR）1.66，95%置信区间（CI）1.39–1.97]。通过遗传学代理的T2D也显著增加了CTS的风险[OR 1.17，95% CI (1.07–1.29)]。在调整其他因素后，BMI和T2D对CTS的因果效应在多变量MR分析中保持一致。我们的中介分析表明，BMI对CTS影响的34.4%是通过T2D介导的。我们还评估了多个BMI和血糖相关特征对CTS的影响。腰围和去脂臂围也与CTS有因果关联。然而，在调整BMI的影响后，这些关联消失了。我们的研究结果表明，肥胖和T2D是CTS的独立风险因素。