Abstract
Background
Inflammation may mediate the co-pathogenesis of rheumatoid arthritis (RA) and depression because inflammatory cytokines are associated with RA and depression. However, traditional observational research was not able to address problems with residual confusion and reverse causality.
Methods
We summarized and retrieved 28 inflammatory cytokines associated with RA, depression, or RA with depression through a literature search. The summary statistics from genome-wide association studies for RA, inflammatory biomarkers, broad depression, and major depression disease phenotypes were used. Mendelian randomization was performed to assess the causal association between RA and inflammatory biomarkers, as well as the effects of inflammatory biomarkers on depression. Bonferroni correction was used to reduce the possibility of false positive results.
Results
The study found that evidence for associations of genetically predicted RA was associated with higher levels of interleukin (IL)-9 (OR = 1.035, 95%CI = 1.002–1.068, P = 0.027), IL-12 (OR = 1.045, 95%CI = 1.045–1.014, P = 0.004), IL-13 (OR = 1.060, 95%CI = 1.028–1.092, P = 0.0001), IL-20 (OR = 1.037, 95%CI = 1.001–1.074, P = 0.047), and IL-27 (OR = 1.017, 95%CI = 1.003–1.032, P = 0.021). The level of IL-7 (OR = 1.029, 95%CI = 1.018–1.436, P = 0.030) was significantly related to RA. Only the analysis results between RA and IL-13 were satisfied with the statistical significance threshold corrected by Bonferroni (P < 0.002). However, a causal effect was not found between inflammatory biomarkers and depression.
Conclusions
In the current study the inflammatory cytokines associated with RA comorbid depression may not be the mediators that directly lead to the co-pathogenesis of RA and depression.
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Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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This work was supported by the National Natural Science Foundation of China (No. 81973778 and 82001710), the National Key R&D Program of China (NO. 2018YFC1705500), and China Postdoctoral Science Foundation (NO. 2022M712850).
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XHD and CPW directed the research, revised the manuscript, and provided final approval of the version to be published. STX and DYX designed the research and wrote the manuscript. YRW contributed to the acquisition of data for the work. STX and YBJ contributed to the analysis and interpretation of data for the work. All authors have read and approved the final manuscript.
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Xiang, S., Xu, D., Jin, Y. et al. The role of inflammatory biomarkers in the association between rheumatoid arthritis and depression: a Mendelian randomization study. Inflammopharmacol 31, 1839–1848 (2023). https://doi.org/10.1007/s10787-023-01241-w
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DOI: https://doi.org/10.1007/s10787-023-01241-w