Unveiling the genetic association between rheumatoid arthritis and four common hand pathologies

Rheumatoid arthritis (RA), carpal tunnel syndrome (CTS), trigger finger (TF), Dupuytren's disease (DD) and de Quervain tenosynovitis (DQT) are musculoskeletal disorders that affect hand abilities. Previous studies have suggested inconsistent results on their association. This study aims to determine the cause-and-effect relationship between RA and other four hand disorders.

We collected summary-level statistics for RA, CTS, TF, DD, and DQT from genome-wide association studies (GWAS). A univariable Mendelian randomization (UVMR) analysis was conducted to investigate the cause-and-effect relationship between RA and other hand conditions. Furthermore, a multivariable Mendelian randomization (MVMR) analysis was conducted to evaluate the influence of confounding variables such as glycemia, obesity, and lifestyle factors on this causal association. The robustness of our findings is assessed by a series of sensitivity analyses at the end.

The inverse variance-weighted method in UVMR revealed that genetically predicted RA was positively associated with risks of CTS (OR = 04, 95% CI 1.01-1.07, P = 4.97E-03), TF (OR = 1.13, 95% CI 1.06-1.20, P = 8.97E-05), and DQT (OR = 1.11, 95% CI  1.02-1.21, P = 0.019), but not linked with DD (OR = 1.01, 95% CI = 0.96-1.07, P = 0.61). After adjusting for glycemia, obesity, and lifestyle factors in the MVMR analyses, the causal effects of RA on increased risks of CTS and TF remained significant. Leave-one-out analyses demonstrated that no individual single nucleotide polymorphism (SNP) significantly impacted RA's overall causal effect estimates on CTS and TF.

Our results indicate that RA is an independent genetic factor contributing to CTS and TF, but not to DQT or DD. This finding supports recommendations aimed at preventing the occurrence of CTS and TF in patients with RA. However, further high-quality studies are needed to validate this association and to determine its general applicability.