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.
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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.
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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.
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U. Müller-Ladner, Bad Nauheim
U. Lange, Bad Nauheim
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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
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DOI: https://doi.org/10.1007/s00393-019-00742-w