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Genetic causal association between rheumatoid arthritis and periodontitis: a bidirectional two-sample Mendelian randomization analysis

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Abstract

Background

A link between rheumatoid arthritis (RA) and periodontitis (PD) has been established. However, their causal relationship remains unclear and the effect of different serotypes of RA on the PD development has not been investigated. This study aims to elucidate the causal association between PD and different serotypes of RA using Mendelian randomization (MR).

Methods

A bidirectional two-sample MR analysis was performed using available large-scale genome-wide association studies statistics. The inverse-variance weighted (IVW) or multiplicative random-effects IVW was used to determine causality, depending on the heterogeneity of instrumental variables. Additional sensitivity analyses were also performed.

Results

The forward MR analysis identified that seropositive RA (odds ratio (OR), 1.26; 95% confidence interval (CI), 1.07–1.44; p = 0.0018), but not seronegative RA (OR, 1.01; 95% CI, 0.95–1.06; p = 0.9098), was associated with an increased risk of PD. The reverse MR analysis did not show any significant causal effect of PD on RA, independent of the serotypes. The sensitivity tests (p > 0.05) confirmed the robustness and accuracy of these findings.

Conclusion

This study revealed that there was a genetic causal effect of seropositive RA on PD, suggesting that this subtype of RA patients may require specific clinical attention to prevent the development of PD.

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Data availability

The data used for analysis were obtained from published studies and public databases. The summary statistics for periodontitis and rheumatoid arthritis can be accessed at https://www.finngen.fi/en.

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Acknowledgements

We would like to express our sincere gratitude to the investigators who generously shared the GWAS summary-level data that were used in this study, as well as to all the participants who took part in the original studies.

Funding

This study was supported by the National Natural Foundation of China (No. 82001048) and Young Elite Scientist Support Program by CSA (No. 2020PYRC001).

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Author notes

  1. Zijian Cheng and Lu Gao contributed equally to this work.

Authors and Affiliations

  1. Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Zhejiang, Hangzhou, China

    Zijian Cheng, Lu Gao, Peng Huang, Dingwen Luo, Chunsheng Bi & Xiaoyan Chen

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  1. Zijian Cheng
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  2. Lu Gao
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  3. Peng Huang
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Contributions

ZC: conceptualization, methodology, data analysis, data curation, writing, funding; LG: conceptualization, methodology, data analysis, data curation, writing; DL, PH, and CB: conceptualization, methodology, writing; XC: conceptualization, writing, supervision, administration. All authors contributed to the article and approved the final submitted version.

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Correspondence to Xiaoyan Chen.

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Ethics approval

This study only included publicly available data and the relevant ethical approval can be found in the corresponding studies.

Competing interests

The authors declare no competing interests.

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What is already known on this topic

Previous epidemiological studies have suggested a link between rheumatoid arthritis (RA) and periodontitis (PD). However, the causal relationship between PD and different serotypes of RA remains unclear.

What this study adds

The application of bidirectional two-sample Mendelian randomization (bi-TSMR) analysis identified that seropositive RA, but not seronegative RA, was associated with an increased risk of PD.

How this study might affect research, practice, or policy

Clinicians should be aware of the importance of periodontal health in RA patients and consider recommending RA patients to undergo periodontal examination or treatment.

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Cheng, Z., Gao, L., Huang, P. et al. Genetic causal association between rheumatoid arthritis and periodontitis: a bidirectional two-sample Mendelian randomization analysis. Clin Oral Invest 28, 107 (2024). https://doi.org/10.1007/s00784-024-05512-w

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