Unraveling the causality between carpal tunnel syndrome and trigger finger through genetic instrumental variables

Carpal tunnel syndrome (CTS) and trigger finger (TF) are the two most common non-traumatic connective tissue disorders of the hands. These conditions often manifest concurrently in certain patients; however, the mechanisms underlying this phenotypic association remain inadequately understood. In this study, we aimed to systematically investigate the causal relationship between CTS and TF using a large sample size and advanced methods.

In this study, comprehensive summary-level data on CTS and TF from genome-wide association studies (GWAS) were collected. The causal relationship between CTS and TF was investigated using two-sample Mendelian randomization (MR). Sensitivity analyses were conducted to evaluate the robustness of MR findings. Furthermore, multivariable Mendelian randomization (MVMR) was employed to examine the role of CTS in causation and adjust for potential confounding variables. Additionally, supplementary reverse MR analysis was performed to ascertain the causal effect of TF on CTS.

Univariate analysis indicated that CTS had a causative influence on TF (OR = 2.53, 95% CI = 1.52-4.23, P = 0.00039). Conversely, reverse MR analyses did not support TF as a causative factor of CTS. Furthermore, in the MVMR analysis, which accounted for potential confounding variables, such as body mass index and type 2 diabetes mellitus, the causal relationship between CTS and TF remained statistically significant and robust.

This study established the genetic causality of CTS on TF, suggesting an elevated risk of TF development in individuals with CTS. These findings may inform evidence-based recommendations aimed at reducing the incidence of TF in patients with CTS.