{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:20:50Z","timestamp":1792790450261,"version":"4.5.0"},"reference-count":38,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T00:00:00Z","timestamp":1674604800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82201062"],"award-info":[{"award-number":["82201062"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Science and technology basic resources","award":["2018FY101004"],"award-info":[{"award-number":["2018FY101004"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"\n Background and Objective<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n 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 (\n Aggregatibacter actinomycetemcomitans<\/jats:italic>\n ), PCT5 (\n Porphyromonas gingivalis<\/jats:italic>\n ), and gingival crevicular fluid (GCF) interleukin-1\n \u03b2<\/jats:italic>\n (IL-1\n \u03b2<\/jats:italic>\n ) 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\n \u03b2<\/jats:italic>\n at statistical significance at genome-wide level (\n P<\/jats:italic>\n \u00a0<\u00a05\u00a0\u00d7\u00a010\n \u22128<\/jats:sup>\n ) were identified as genetic instruments. We used two-sample summary MR methods and tested the existence of a pleiotropic effect with MR-Egger.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n 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\u20131.05),\n P<\/jats:italic>\n \u00a0=\u00a00.0171; ebi-a-GCST010777: OR = 1.03 (95% CI, 1.00\u20131.05),\n P<\/jats:italic>\n \u00a0=\u00a00.0397). 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\n \u03b2<\/jats:italic>\n ) on COVID-19 risk across the two datasets (ebi-a-GCST010776: IVW OR = 1.02 (95% CI, [1.01\u20131.03]),\n P<\/jats:italic>\n \u00a0<\u00a00.001; ebi-a-GCST010777: IVW OR = 1.03 (95% CI, [1.02\u20131.04]),\n P<\/jats:italic>\n \u00a0<\u00a00.001). The intercepts of MR-Egger yielded no proof for significant directional pleiotropy for either dataset (ebi-a-GCST010776:\n P<\/jats:italic>\n \u00a0=\u00a00.7660; ebi-a-GCST010777:\n P<\/jats:italic>\n \u00a0=\u00a00.6017).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n The findings suggests that periodontitis and the higher GCF IL-1\n \u03b2<\/jats:italic>\n 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.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.7717\/peerj.14595","type":"journal-article","created":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T04:50:10Z","timestamp":1674622210000},"page":"e14595","source":"Crossref","is-referenced-by-count":12,"title":["Association between periodontitis and COVID-19 infection: a two-sample Mendelian randomization study"],"prefix":"10.7717","volume":"11","author":[{"given":"Zhaoqiang","family":"Meng","sequence":"first","affiliation":[{"name":"Beijing Laboratory of Biomedical Materials, Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujia","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing Laboratory of Biomedical Materials, Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, China"},{"name":"Peking University Health Science Center, Institute of Medical Technology, Beijing, P. R. China"},{"name":"Key Laboratory of Dental Material, National Medical Products Administration, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuliang","family":"Deng","sequence":"additional","affiliation":[{"name":"Beijing Laboratory of Biomedical Materials, Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, China"},{"name":"Key Laboratory of Dental Material, National Medical Products Administration, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4443","published-online":{"date-parts":[[2023,1,25]]},"reference":[{"issue":"4","key":"10.7717\/peerj.14595\/ref-1","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1002\/JPER.21-0272","article-title":"A case-control study on the association between periodontitis and coronavirus disease (COVID-19)","volume":"93","author":"Anand","year":"2021","journal-title":"Journal of 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