Beijing Laboratory of Biomedical Materials, Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, China.
Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, P. R. China.
PeerJ. 2023 Jan 25;11:e14595. doi: 10.7717/peerj.14595. eCollection 2023.
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.
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 (), PCT5 (), and gingival crevicular fluid (GCF) interleukin-1 (IL-1) 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-1 at statistical significance at genome-wide level ( < 5 × 10) were identified as genetic instruments. We used two-sample summary MR methods and tested the existence of a pleiotropic effect with MR-Egger.
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), = 0.0171; ebi-a-GCST010777: OR = 1.03 (95% CI, 1.00-1.05), = 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-1) on COVID-19 risk across the two datasets (ebi-a-GCST010776: IVW OR = 1.02 (95% CI, [1.01-1.03]), < 0.001; ebi-a-GCST010777: IVW OR = 1.03 (95% CI, [1.02-1.04]), < 0.001). The intercepts of MR-Egger yielded no proof for significant directional pleiotropy for either dataset (ebi-a-GCST010776: = 0.7660; ebi-a-GCST010777: = 0.6017).
The findings suggests that periodontitis and the higher GCF IL-1 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.
流行病学研究报告了 2019 年冠状病毒病（COVID-19）与牙周炎之间的关联；然而，尚未证明其因果关系。本研究旨在通过两样本孟德尔随机化（MR）分析评估 COVID-19 易感性与牙周炎之间的关联。
使用欧洲血统人群的 OpenGWAS 数据库中的结果和暴露数据进行两样本汇总 MR 分析。牙周复合特征（PCTs）被选为牙周炎表型的替代物。考虑了 PCT3（）、PCT5（）和龈沟液（GCF）白细胞介素-1（IL-1）与 COVID-19 之间的因果关联。选择了两个最大样本量的全基因组关联研究（GWAS）数据集作为 COVID-19 结果（数据集 ebi-a-GCST010776 和 ebi-a-GCST010777）。在全基因组水平上具有统计学意义的与 PCT3、PCT5 和 GCF IL-1 相关的单核苷酸多态性（SNPs）（<5×10）被确定为遗传工具。我们使用两样本汇总 MR 方法，并使用 MR-Egger 测试了存在偏倚的可能性。
反向方差加权（IVW）估计表明，COVID-19 风险与牙周炎之间存在正相关（ebi-a-GCST010776：比值比[OR] = 1.02（95%置信区间[CI]，1.00-1.05），<0.0017；ebi-a-GCST010777：OR = 1.03（95% CI，1.00-1.05），<0.0017）。加权中位数也显示出方向相似的估计值。对其他 PCTs 与 COVID-19 之间的因果关系的探索发现，局部炎症反应（GCF IL-1）对 COVID-19 风险有轻微影响，这在两个数据集上均得到了证实（ebi-a-GCST010776：IVW OR = 1.02（95% CI，[1.01-1.03]），<0.001；ebi-a-GCST010777：IVW OR = 1.03（95% CI，[1.02-1.04]），<0.001）。MR-Egger 的截距没有为任何数据集提供显著方向性偏倚的证据（ebi-a-GCST010776：= 0.7660；ebi-a-GCST010777：= 0.6017）。
研究结果表明，牙周炎和更高水平的 GCF IL-1 与 COVID-19 易感性增加有关。然而，鉴于我们研究的局限性，需要进行精心设计的随机对照试验来证实其发现，这可能代表一种预防 COVID-19 的新的非药物干预措施。
