Association between periodontitis and COVID-19 infection: a two-sample Mendelian randomization study

Zhaoqiang Meng; Yujia Ma; Wenjing Li; Xuliang Deng

doi:10.7717/peerj.14595

Association between periodontitis and COVID-19 infection: a two-sample Mendelian randomization study

PeerJ. 2023 Jan 25:11:e14595. doi: 10.7717/peerj.14595. eCollection 2023.

Authors

Zhaoqiang Meng^#¹, Yujia Ma^#², Wenjing Li^{1

3

4}, Xuliang Deng^{1

4}

Affiliations

¹ Beijing Laboratory of Biomedical Materials, Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, China.
² Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, P. R. China.
³ Peking University Health Science Center, Institute of Medical Technology, Beijing, P. R. China.
⁴ Key Laboratory of Dental Material, National Medical Products Administration, Beijing, China.

^# Contributed equally.

Abstract

Background and objective: Epidemiological studies report associations between coronavirus disease 2019 (COVID-19) and periodontitis; however, causality has not been proven. The aim of this study is to assess the associations between COVID-19 susceptibility and periodontitis with two-sample Mendelian randomization (MR) analyses.

Methods: A two-sample summary MR analysis was performed using data for outcome and exposure from the OpenGWAS database on people of European descent. Periodontal complex traits (PCTs) were chosen as a proxy for the periodontitis phenotype. The causal association between PCT3 (Aggregatibacter actinomycetemcomitans), PCT5 (Porphyromonas gingivalis), and gingival crevicular fluid (GCF) interleukin-1β (IL-1β) and COVID-19 were considered. Genome-wide association study (GWAS) data with the two largest sample sizes were selected as COVID-19 outcomes (datasets ebi-a-GCST010776 and ebi-a-GCST010777). Single-nucleotide polymorphisms (SNPs) associated with PCT3, PCT5, and GCF IL-1β at statistical significance at genome-wide level (P < 5 × 10^-8) were identified as genetic instruments. We used two-sample summary MR methods and tested the existence of a pleiotropic effect with MR-Egger.

Results: Inverse-variance weighted (IVW) estimates showed that there was a positive association between COVID-19 risk and periodontitis (ebi-a-GCST010776: odds ratio [OR] = 1.02 (95% confidence interval (CI), 1.00-1.05), P = 0.0171; ebi-a-GCST010777: OR = 1.03 (95% CI, 1.00-1.05), P = 0.0397). The weighted median also showed directionally similar estimates. Exploration of the causal associations between other PCTs and COVID-19 identified a slight effect of local inflammatory response (GCF IL-1β) on COVID-19 risk across the two datasets (ebi-a-GCST010776: IVW OR = 1.02 (95% CI, [1.01-1.03]), P < 0.001; ebi-a-GCST010777: IVW OR = 1.03 (95% CI, [1.02-1.04]), P < 0.001). The intercepts of MR-Egger yielded no proof for significant directional pleiotropy for either dataset (ebi-a-GCST010776: P = 0.7660; ebi-a-GCST010777: P = 0.6017).

Conclusions: The findings suggests that periodontitis and the higher GCF IL-1β levels is causally related to increase susceptibility of COVID-19. However, given the limitations of our study, the well-designed randomized controlled trials are needed to confirm its findings, which may represent a new non-pharmaceutical intervention for preventing COVID-19.

Keywords: COVID-19; Mendelian randomization; Periodontitis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

COVID-19* / epidemiology
Causality
Genome-Wide Association Study
Humans
Mendelian Randomization Analysis
Periodontitis* / epidemiology

Grants and funding

This work was supported by the National Natural Science Foundation of China (82201062) and the National Science and Technology basic resources project (2018FY101004). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.