Assessment of bidirectional relationships between depression and rheumatoid arthritis among adults: a two-sample...

Increasing evidence shows that depression is associated with rheumatoid arthritis (RA). However, the causality and direction of this association remain unclear, because links between the two diseases might be caused by shared environmental confounding factors. Our study aims to understand a putative causal link between the two diseases.

We retrieved summary statistics from meta-analyses of non-overlapping genome-wide association studies (GWASes) for depression (n = 807,553, 246,363 cases and 561,190 controls) and RA (n = 58,284, 14,361 cases and 42,923 controls). We combined Mendelian randomization (MR) estimates from each genetic instrument using inverse-variance weighted (IVW) meta-analysis, with alternate methods (e.g., simple median approach, weighted median approach, and MR-Egger regression) and conducted sensitivity analyses to assess the robustness of MR analyses.

We found no evidence of causal relationships between depression and RA across all MR methods (IVW OR, 1.028 for RA; 95% CI, 0.821-1.287; P = 0.810) or vice versa (IVW OR, 0.999 for depression; 95% CI, 0.984-1.014; P = 0.932), indicating the links between the two diseases might be due to confounders.

Despite the results, to optimize treatment outcomes of RA patients, we still emphasize depression should be managed as part of routine clinical care to optimize treatment outcomes of RA.