Skip to main content
SpringerLink
Log in

Causal association between periodontitis and risk of rheumatoid arthritis and systemic lupus erythematosus: a Mendelian randomization

Kausalzusammenhang zwischen Periodontitis und dem Risiko für rheumatoide Arthritis und systemischen Lupus erythematodes: eine Mendel-Randomisierung

  • Original articles
  • Published:
Zeitschrift für Rheumatologie Aims and scope Submit manuscript

Abstract

Objective

To investigate whether periodontitis is causally associated with risk of rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE).

Methods

We performed two-sample Mendelian randomization (MR) analysis using the inverse variance-weighted (IVW), weighted median, and MR-Egger regression methods on publicly available summary statistics datasets using a periodontitis genome-wide association study (GWAS) as an exposure and RA and SLE GWASs on individuals of European descent as outcomes.

Results

We selected 7 or 20 single-nucleotide polymorphisms from a periodontitis GWAS as instrumental variables for RA or SLE. The IVW method results support a causal association between periodontitis and RA (beta = 0.168, SE = 0.080, p = 0.035) and SLE (beta = 0.0001, SE = 0.0001, p = 0.046) risk; however, the weighted median approach did not indicate a significant causal association. MR-Egger regression revealed that directional pleiotropy was unlikely to be biasing the RA (intercept = −0.115, p = 0.078) or SLE results (intercept = 4.68E-05, p = 0.394); no significant causal association was found between periodontitis and RA and SLE. The MR estimates from the IVW, weighted median, and MR-Egger regression analyses were not consistent.

Conclusion

Only the results of MR analysis by the IVW method indicated that periodontitis is likely causally associated with an increased risk of RA and SLE incidence. Our MR showed weak causal association between periodontitis and RA or SLE. These findings may assist in elucidating the underlying mechanisms of the effects of periodontitis on RA and SLE incidence.

Zusammenfassung

Ziel

Es wurde untersucht, ob Parodontitis kausal mit dem Risiko von rheumatoider Arthritis (RA) oder systemischem Lupus erythematodes (SLE) assoziiert ist.

Methoden

Es erfolgte eine mendelsche Randomisierungsanalyse (MR) mit zwei Stichproben. Dabei wurden Methoden der Inverse-Varianz-Gewichtung, des gewichteten Medians und der MR-Egger-Regression auf öffentlich zugängliche Datensätze von Maßzahlen angewendet, wobei eine genomweite Assoziationsstudie (GWAS) zu Parodontitis als Exposition sowie RA- und SLE-GWAS an Personen europäischer Abstammung als Outcome dienten.

Ergebnisse

Die Autoren wählten 7 bzw. 20 Einzelnukleotidpolymorphismen aus einer Periodontitis-GWAS als instrumentelle Variablen für RA bzw. SLE aus. Die Ergebnisse der IVW-Methode unterstützen einen kausalen Zusammenhang zwischen Periodontitis und RA- (β = 0,168; Standardfehler, „standard error“, SE = 0,080; p = 0,035) sowie SLE-Risiko (β = 0,0001; SE = 0,0001; p = 0,046); der Ansatz unter Verwendung des gewichteten Mittels jedoch ergab keinen Hinweis auf einen signifikanten kausalen Zusammenhang. Die MR-Egger-Regression zeigte, dass es unwahrscheinlich war, dass die direktionale Pleiotropie eine Quelle für Bias bei den Ergebnissen für RA (Intercept = −0,115; p = 0,078) oder SLE (Intercept =4,68*10−5; p = 0,394) darstellte, aber sie ergab keinen Kausalzusammenhang zwischen Periodontitis und RA sowie SLE. Die MR-Schätzwerte aus den Verfahren mit IVW, gewichtetem Mittel und der MR-Egger-Regressionsanalyse waren nicht konsistent.

Schlussfolgerung

Nur die Ergebnisse der MR-Analyse unter Verwendung der IVW-Methode zeigten, dass eine Periodontitis wahrscheinlich kausal mit einem erhöhten Risiko für die Inzidenz von RA und SLE verknüpft ist. Die vorliegende MR ergab einen schwachen kausalen Zusammenhang zwischen Periodontitis und RA oder SLE. Diese Befunde tragen möglicherweise dazu bei, die zugrunde liegenden Mechanismen der Auswirkungen einer Periodontitis auf die Inzidenz von RA und SLE zu erhellen.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Bae S‑C, Lee Y (2018) Association between anti-porphyromonas gingivalis antibody, anti-citrullinated protein antibodies, and rheumatoid arthritis. Z Rheumatol 77(6):522–532

    Article  CAS  Google Scholar 

  2. Bowden J, Davey Smith G, Burgess S (2015) Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol 44(2):512–525

    Article  Google Scholar 

  3. Bowden J, Davey Smith G, Haycock PC et al (2016) Consistent estimation in Mendelian randomization with some invalid instruments using a weighted median estimator. Genet Epidemiol 40(4):304–314

    Article  Google Scholar 

  4. Burgess S, Butterworth A, Thompson SG (2013) Mendelian randomization analysis with multiple genetic variants using summarized data. Genet Epidemiol 37(7):658–665

    Article  Google Scholar 

  5. Burgess S, Daniel RM, Butterworth AS et al (2014) Network Mendelian randomization: using genetic variants as instrumental variables to investigate mediation in causal pathways. Int J Epidemiol 44(2):484–495

    Article  Google Scholar 

  6. Burgess S, Thompson SG (2017) Interpreting findings from Mendelian randomization using the MR-Egger method. Eur J Epidemiol 32(5):377–389

    Article  Google Scholar 

  7. Burgess S, Thompson SG, CRP CHD Genetics Collaboration (2011) Avoiding bias from weak instruments in Mendelian randomization studies. Int J Epidemiol 40(3):755–764

    Article  Google Scholar 

  8. Cekici A, Kantarci A, Hasturk H et al (2014) Inflammatory and immune pathways in the pathogenesis of periodontal disease. Periodontol 2000 64(1):57–80

    Article  Google Scholar 

  9. de Oliveira Ferreira R, de Brito Silva R, Magno MB et al (2019) Does periodontitis represent a risk factor for rheumatoid arthritis? A systematic review and meta-analysis. Therapeutic Advances in Musculoskeletal 11:1759720X19858514

    Article  Google Scholar 

  10. de Souza S, Bansal R, Galloway J (2016) Rheumatoid arthritis—an update for general dental practitioners. Br Dent J 221(10):667

    Article  Google Scholar 

  11. Egger M, Smith GD, Phillips AN (1997) Meta-analysis: principles and procedures. BMJ 315(7121):1533–1537

    Article  CAS  Google Scholar 

  12. Fuggle NR, Smith TO, Kaul A et al (2016) Hand to mouth: a systematic review and meta-analysis of the association between rheumatoid arthritis and periodontitis. Front Immunol 7:80. https://doi.org/10.3389/fimmu.2016.00080

    Article  CAS  Google Scholar 

  13. Hartwig FP, Davies NM, Hemani G et al (2016) Two-sample Mendelian randomization: avoiding the downsides of a powerful, widely applicable but potentially fallible technique. Int J Epidemiol 45(6):1717–1726. https://doi.org/10.1093/ije/dyx028

    Article  Google Scholar 

  14. Hemani G, Zheng J, Wade K et al (2016) MR-Base: a platform for systematic causal inference across the phenome using billions of genetic associations. bioRxiv. https://doi.org/10.1101/078972

    Article  Google Scholar 

  15. Hill HA, Kleinbaum DG (2000) Bias in observational studies. Encyclopedia of biostatistics

    Google Scholar 

  16. Lee YH (2018) Association between the neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio and rheumatoid arthritis and their correlations with the disease activity: a meta-analysis. J Rheum Dis 25(3):169–178

    Article  Google Scholar 

  17. Lee YH (2015) Meta-analysis of genetic association studies. Ann Lab Med 35(3):283–287

    Article  CAS  Google Scholar 

  18. Lee YH, Bae S‑C, Choi SJ et al (2012) Genome-wide pathway analysis of genome-wide association studies on systemic lupus erythematosus and rheumatoid arthritis. Mol Biol Rep 39(12):10627–10635

    Article  CAS  Google Scholar 

  19. Lee YH, Song GG (2019) Causal association between rheumatoid arthritis with the increased risk of type 2 diabetes: a mendelian randomization analysis. J Rheum Dis 26(2):131–136

    Article  Google Scholar 

  20. Pierce BL, Burgess S (2013) Efficient design for Mendelian randomization studies: subsample and 2‑sample instrumental variable estimators. Am J Epidemiol 178(7):1177–1184

    Article  Google Scholar 

  21. Rutter-Locher Z, Smith TO, Giles I et al (2017) Association between systemic lupus erythematosus and periodontitis: a systematic review and meta-analysis. Front Immunol 8:1295

    Article  Google Scholar 

  22. Song GG, Bae S‑C, Lee YH (2012) Association between vitamin D intake and the risk of rheumatoid arthritis: a meta-analysis. Baillieres Clin Rheumatol 31(12):1733–1739

    Article  Google Scholar 

  23. Stahl EA, Raychaudhuri S, Remmers EF et al (2010) Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci. Nat Genet 42(6):508

    Article  CAS  Google Scholar 

  24. Swerdlow DI, Kuchenbaecker KB, Shah S et al (2016) Selecting instruments for Mendelian randomization in the wake of genome-wide association studies. Int J Epidemiol 45(5):1600–1616

    Article  Google Scholar 

  25. Teumer A, Holtfreter B, Volker U et al (2013) Genome-wide association study of chronic periodontitis in a general German population. J Clin Periodontol 40(11):977–985

    Article  CAS  Google Scholar 

Download references

Funding

This study was supported in part by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science & ICT (NRF-2017M3A9B4050335), Republic of Korea.

Author information

Authors and Affiliations

  1. Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea (Republic of)

    S.-C. Bae

  2. Department of Rheumatology, Korea University Anam Hospital, Korea University College of Medicine, 73, Inchon-ro, Seongbuk-gu, 02841, Seoul, Korea (Republic of)

    Y. H. Lee MD, PhD

Authors
  1. S.-C. Bae
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y. H. Lee MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Y. H. Lee MD, PhD.

Ethics declarations

Conflict of interest

S.-C. Bae and Y.H. Lee declare that they have no competing interests.

For this article no studies with human participants or animals were performed by any of the authors. All studies performed were in accordance with the ethical standards indicated in each case.

Additional information

Redaktion

U. Müller-Ladner, Bad Nauheim

U. Lange, Bad Nauheim

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bae, SC., Lee, Y.H. Causal association between periodontitis and risk of rheumatoid arthritis and systemic lupus erythematosus: a Mendelian randomization. Z Rheumatol 79, 929–936 (2020). https://doi.org/10.1007/s00393-019-00742-w

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00393-019-00742-w

Keywords

Schlüsselwörter

Search

Navigation