Causal relationship between thyroid dysfunction and carpal tunnel syndrome: a bidirectional Mendelian randomization study

Abstract ObjectiveTo investigate the bidirectional causal relationship between thyroid dysfunction (including hypothyroidism and hyperthyroidism) and carpal tunnel syndrome using Mendelian randomization (MR). Methods In forward MR, hypothyroidism and hyperthyroidism were exposed and carpal tunnel syndrome was the outcome. Reverse MR Showed carpal tunnel syndrome as exposure, hypothyroidism and hyperthyroidism as outcome. Genetic loci independently associated with hypothyroidism, hyperthyroidism, and carpal tunnel syndrome were selected as instrumental variables (IV) from aggregated data from genome-wide association studies (GWAS). Inverse variance weighting (IVW) was used to analyze the causal effect, supplemented by weighted median (WME) and MR-Egger. Heterogeneity test, pleiotropy test and Leave-one-out method were used for sensitivity analysis to explore the robustness of the results. Results Both hypothyroidism and hyperthyroidism increased the risk of carpal tunnel syndrome (hypothyroidism: IVW,OR=1.04,95%CI= 1.01-1.08, P=0.017; Hyperthyroidism: IVW,OR=1.08,95%CI= 1.05-1.12, P= 9.218e-06), no pleiotropy was found in both tests. There was no causal association between hypothyroidism (IVW:OR=1.20,95%CI=0.80-1.81, P=0.373) and hyperthyroidism (IVW:OR=1.40,95%CI=0.74-2.63P=1.398), and no pleiotropy was found between the two. Conclusion Patients with thyroid dysfunction have an increased risk of carpal tunnel syndrome. Carpal tunnel syndrome has no significant effect on hypothyroidism and hyperthyroidism.