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

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Abstract

Objective

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.

Methods

We retrieved summary statistics from meta-analyses of non-overlap** 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.

Results

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.

Conclusion

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.

Key Points

• This is the first MR study to evaluate the causal association between depression and RA.

• MR analyses do not support causal associations between depression and RA.

• The links between depression and RA witnessed in observational studies might be due to environmental confounders.

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Data availability

The original data presented in the study are included in the supplementary material, and further inquiries can be directed to the corresponding authors.

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Acknowledgements

We gratefully thank these authors [10, 11] for providing summary statistics used in our MR study.

Funding

This work was supported by the Primary Research Project of Traditional Chinese Medicine in Zhejiang Province (No. 2021ZZ015) and the Scientific Research Project of Traditional Chinese Medicine in Zhejiang Province (No. 2022ZB174 and 2021ZB151).

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Author notes

  1. Sijia Fang and Shuo Huang have contributed equally to this work and shared first authorship.

Authors and Affiliations

  1. Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China

    Sijia Fang

  2. The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China

    Shuo Huang, Fengyuan Tian & Yaxue Han

  3. The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China

    Kepeng Yang

  4. The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China

    Qin Zhang

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  1. Sijia Fang
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Contributions

Conceptualization, Qin Zhang and Kepeng Yang; methodology, Sijia Fang and Shuo Huang; software, Shuo Huang; formal analysis, Shuo Huang; resources, Sijia Fang; data curation, Fengyuan Tian and Yaxue Han; writing—original draft preparation, Sijia Fang; writing—review and editing, Fengyuan Tian and Yaxue Han; supervision, Qin Zhang. All authors have read and agreed to the published version of the manuscript.

Corresponding authors

Correspondence to Kepeng Yang or Qin Zhang.

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Ethical review and approval were waived for this study, as all data used for this study are publicly available and their original studies are cited. All these studies obtained relevant participant consent and ethical approval.

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Fang, S., Huang, S., Tian, F. et al. Assessment of bidirectional relationships between depression and rheumatoid arthritis among adults: a two-sample Mendelian randomization study. Clin Rheumatol 42, 1039–1046 (2023). https://doi.org/10.1007/s10067-022-06455-x

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