Non-Cochrane · aetiology · PM41618286
Causal association between periodontitis and systemic diseases: a systematic review and meta-analysis of mendelian randomization studies.
Zhao Yanghao, Zhang Churen, Chang Xiaochi, et al. · BMC oral health · 2026 · PubMed · doi:10.1186/s12903-026-07725-9
Findings
Population Populations in Mendelian randomization GWAS studies (mostly European ancestry)
30 findings
| Genetically predicted periodontitis (MR exposure) | Lower genetic liability to periodontitis | Hypothyroidism MR-Egger estimator | No significant causal relationship (MR-Egger); pooled estimate not legible in figure GRADE not reported 3 studies |
| Genetically predicted periodontitis (MR exposure) | Lower genetic liability to periodontitis | Non-alcoholic fatty liver disease IVW estimator | OR 1.10 [1.04, 1.17] GRADE not reported 4 studies |
| Genetically predicted periodontitis (MR exposure) | Lower genetic liability to periodontitis | Ulcerative colitis IVW estimator | No significant causal relationship (IVW); pooled estimate not legible in figure GRADE not reported 8 studies |
| Genetically predicted periodontitis (MR exposure) | Lower genetic liability to periodontitis | Non-alcoholic fatty liver disease MR-Egger estimator | OR 1.09 [0.99, 1.22] GRADE not reported 4 studies |
| Genetically predicted periodontitis (MR exposure) | Lower genetic liability to periodontitis | Small vessel stroke IVW estimator | OR 1.00 [0.97, 1.03] GRADE not reported 7 studies |
| Genetically predicted periodontitis (MR exposure) | Lower genetic liability to periodontitis | Diabetes MR-Egger estimator | OR 0.99 [0.96, 1.03] GRADE not reported 6 studies |
| Genetically predicted periodontitis (MR exposure) | Lower genetic liability to periodontitis | Coronary atherosclerosis IVW estimator | OR 1.00 [1.00, 1.00] GRADE not reported 6 studies |
| Genetically predicted periodontitis (MR exposure) | Lower genetic liability to periodontitis | Sjogren's syndrome IVW estimator | No significant causal relationship (IVW); pooled estimate not legible in figure GRADE not reported 5 studies |
| Genetically predicted periodontitis (MR exposure) | Lower genetic liability to periodontitis | Sjogren's syndrome MR-Egger estimator | No significant causal relationship (MR-Egger); pooled estimate not legible in figure GRADE not reported 3 studies |
| Genetically predicted periodontitis (MR exposure) | Lower genetic liability to periodontitis | Depression IVW estimator | OR 1.02 [1.00, 1.05] GRADE not reported 3 studies |
| Genetically predicted periodontitis (MR exposure) | Lower genetic liability to periodontitis | Gastric cancer MR-Egger estimator | No significant causal relationship (MR-Egger); pooled estimate not legible in figure GRADE not reported 4 studies |
| Genetically predicted periodontitis (MR exposure) | Lower genetic liability to periodontitis | Rheumatoid arthritis MR-Egger estimator | No significant causal relationship (MR-Egger); pooled estimate not legible in figure GRADE not reported 7 studies |
| Genetically predicted periodontitis (MR exposure) | Lower genetic liability to periodontitis | Inflammatory bowel disease MR-Egger estimator | No significant causal relationship (MR-Egger); pooled estimate not legible in figure GRADE not reported 5 studies |
| Genetically predicted periodontitis (MR exposure) | Lower genetic liability to periodontitis | Parkinson's disease MR-Egger estimator | OR 1.00 [1.00, 1.00] GRADE not reported 3 studies |
| Genetically predicted periodontitis (MR exposure) | Lower genetic liability to periodontitis | Parkinson's disease IVW estimator | OR 1.00 [1.00, 1.00] GRADE not reported 3 studies |
| Genetically predicted periodontitis (MR exposure) | Lower genetic liability to periodontitis | Crohn's disease IVW estimator | No significant causal relationship (IVW); pooled estimate not legible in figure GRADE not reported 5 studies |
| Genetically predicted periodontitis (MR exposure) | Lower genetic liability to periodontitis | Ulcerative colitis MR-Egger estimator | No significant causal relationship (MR-Egger); pooled estimate not legible in figure GRADE not reported 6 studies |
| Genetically predicted periodontitis (MR exposure) | Lower genetic liability to periodontitis | Gastric cancer IVW estimator | No significant causal relationship (IVW); pooled estimate not legible in figure GRADE not reported 4 studies |
| Genetically predicted periodontitis (MR exposure) | Lower genetic liability to periodontitis | Psoriasis IVW estimator | OR 1.00 [1.00, 1.01] GRADE not reported 4 studies |
| Genetically predicted periodontitis (MR exposure) | Lower genetic liability to periodontitis | Crohn's disease MR-Egger estimator | No significant causal relationship (MR-Egger); pooled estimate not legible in figure GRADE not reported 4 studies |
| Genetically predicted periodontitis (MR exposure) | Lower genetic liability to periodontitis | Cardioembolic stroke IVW estimator | OR 1.03 [1.00, 1.05] GRADE not reported 7 studies |
| Genetically predicted periodontitis (MR exposure) | Lower genetic liability to periodontitis | Ischemic stroke IVW estimator | OR 1.00 [0.99, 1.01] GRADE not reported 7 studies |
| Genetically predicted periodontitis (MR exposure) | Lower genetic liability to periodontitis | Stroke (any) IVW estimator | OR 0.99 [0.98, 1.01] GRADE not reported 5 studies |
| Genetically predicted periodontitis (MR exposure) | Lower genetic liability to periodontitis | Inflammatory bowel disease IVW estimator | No significant causal relationship (IVW); pooled estimate not legible in figure GRADE not reported 7 studies |
| Genetically predicted periodontitis (MR exposure) | Lower genetic liability to periodontitis | Alzheimer's disease MR-Egger estimator | OR 0.98 [0.94, 1.03] GRADE not reported 3 studies |
| Genetically predicted periodontitis (MR exposure) | Lower genetic liability to periodontitis | Diabetes IVW estimator | OR 1.02 [1.00, 1.03] GRADE not reported 6 studies |
| Genetically predicted periodontitis (MR exposure) | Lower genetic liability to periodontitis | Alzheimer's disease IVW estimator | OR 1.01 [0.98, 1.05] GRADE not reported 4 studies |
| Genetically predicted periodontitis (MR exposure) | Lower genetic liability to periodontitis | Hyperthyroidism IVW estimator | No significant causal relationship (IVW); pooled estimate not legible in figure GRADE not reported 5 studies |
| Genetically predicted periodontitis (MR exposure) | Lower genetic liability to periodontitis | Rheumatoid arthritis IVW estimator | No significant causal relationship (IVW); pooled estimate not legible in figure GRADE not reported 7 studies |
| Genetically predicted periodontitis (MR exposure) | Lower genetic liability to periodontitis | Hypothyroidism IVW estimator | No significant causal relationship (IVW); pooled estimate not legible in figure GRADE not reported 5 studies |
Included primary studies 58
Open in Studies| Study | Year | Also included by | Outcomes it informs here | Trial data |
|---|---|---|---|---|
| Bae SC 2020 Causal association between periodontitis and risk of rheumatoid arthritis and systemic lupus erythematosus: a Mendelian randomization DOI:10.1007/s00393-019-00742-w | 2020 | this review only | not stated | not extracted yet |
| Bae, SC., Lee, Y.H. ,2020 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Baurecht H 2022 Relationship between periodontitis and psoriasis: A two‐sample Mendelian randomization study DOI:10.1111/jcpe.13620 | 2022 | this review only | not stated | not extracted yet |
| Bell S 2020 Is periodontitis a risk factor for ischaemic stroke, coronary artery disease and subclinical atherosclerosis? A Mendelian randomization… DOI:10.1016/j.atherosclerosis.2020.09.029 | 2020 | this review only | not stated | not extracted yet |
| Bell S et al.,2020 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Botelho J 2021 Causal Association between Periodontitis and Parkinson’s Disease: A Bidirectional Mendelian Randomization Study DOI:10.3390/genes12050772 | 2021 | this review only | not stated | not extracted yet |
| Botelho J. et al.,2021 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| C Sheng et al.,2024 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Cheng X 2024 DOI:10.3290/j.ohpd.b5395053 | NR | this review only | not stated | not extracted yet |
| Cheng Xiaofan et al.,2024 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Cheng Z 2024 Genetic causal association between rheumatoid arthritis and periodontitis: a bidirectional two-sample Mendelian randomization analysis DOI:10.1007/s00784-024-05512-w | 2024 | this review only | not stated | not extracted yet |
| Deng Z 2024 No genetic causal associations between periodontitis and brain atrophy or cognitive impairment: evidence from a comprehensive… DOI:10.1186/s12903-024-04367-7 | 2024 | this review only | not stated | not extracted yet |
| Deng, Z. et al.,2024 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Fan JC 2024 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Feng Qiao et al.,2023 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Gao Y 2024 Periodontitis and thyroid function: A bidirectional Mendelian randomization study DOI:10.1111/jre.13240 | 2024 | this review only | not stated | not extracted yet |
| Hansjörg Baurecht et al.,2022 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Hu C 2024 Periodontal disease and risk of Alzheimer's disease: A two‐sample Mendelian randomization DOI:10.1002/brb3.3486 | 2024 | this review only | not stated | not extracted yet |
| Hu Z 2024 Depression, stress-related disorders and risk for dental caries and periodontitis: A bidirectional and multivariable Mendelian… DOI:10.1016/j.jad.2024.06.026 | 2024 | this review only | not stated | not extracted yet |
| Jun Xiong et al.,2024 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Li Tan et al.,2023 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Li Z 2024 A Mendelian Randomisation Analysis Reveals No Relationship Between Periodontitis and Coronary Atherosclerosis DOI:10.1016/j.identj.2024.01.027 | 2024 | this review only | not stated | not extracted yet |
| Liu Y 2024 Periodontitis and Sjogren’s syndrome: a bidirectional two-sample mendelian randomization study DOI:10.1186/s12903-024-04151-7 | 2024 | this review only | not stated | not extracted yet |
| Ma C 2023 Periodontitis and stroke: A Mendelian randomization study DOI:10.1002/brb3.2888 | 2023 | this review only | not stated | not extracted yet |
| Mi S 2024 Two-sample Mendelian randomization analysis of the relationship between periodontitis and risk of upper gastrointestinal cancers DOI:10.1093/postmj/qgae069 | 2024 | this review only | not stated | not extracted yet |
| Nolde M 2022 No bidirectional relationship between depression and periodontitis: A genetic correlation and Mendelian randomization study DOI:10.3389/fimmu.2022.918404 | 2022 | this review only | not stated | not extracted yet |
| Nolde Michael et al.,2022 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Pi Y 2024 Genetic evidence strengthens the bidirectional connection between oral health status and psychiatric disorders: A two-sample Mendelian… DOI:10.1016/j.jad.2024.01.232 | 2024 | this review only | not stated | not extracted yet |
| Qiao F 2023 Periodontitis and <scp>NAFLD</scp>‐related diseases: A bidirectional two‐sample Mendelian randomization study DOI:10.1111/odi.14785 | 2023 | this review only | not stated | not extracted yet |
| Qing X 2024 Causal Association Analysis of Periodontitis and Inflammatory Bowel Disease: A Bidirectional Mendelian Randomization Study DOI:10.1093/ibd/izad188 | 2024 | this review only | not stated | not extracted yet |
| Rui Zhang,2024 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Shah Parth D.,2021 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Shah PD 2021 Impact of Liability to Periodontitis on Glycemic Control and Type II Diabetes Risk: A Mendelian Randomization Study DOI:10.3389/fgene.2021.767577 | 2021 | this review only | not stated | not extracted yet |
| Sheng C 2024 Periodontitis and the risk of oral, gastric and esophageal cancers: a two‐sample Mendelian randomization study DOI:10.1111/adj.13028 | 2024 | this review only | not stated | not extracted yet |
| Shuyi Mi et al.,2024 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Sun YQ 2020 Mixed evidence for the relationship between periodontitis and Alzheimer’s disease: A bidirectional Mendelian randomization study DOI:10.1371/journal.pone.0228206 | 2020 | this review only | not stated | not extracted yet |
| Tan L 2023 A Mendelian randomization study between chronic periodontitis and non‐alcoholic fatty liver disease DOI:10.1111/jre.13218 | 2023 | this review only | not stated | not extracted yet |
| Wang YB 2022 Causal Association Between Periodontitis and Type 2 Diabetes: A Bidirectional Two-Sample Mendelian Randomization Analysis DOI:10.3389/fgene.2021.792396 | 2022 | this review only | not stated | not extracted yet |
| Wang YB,2022 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Wang Z 2023 Association between inflammatory bowel disease and periodontitis: A bidirectional two‐sample Mendelian randomization study DOI:10.1111/jcpe.13782 | 2023 | this review only | not stated | not extracted yet |
| Xiangli Qing,2024 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Xie P 2024 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Xiong J 2024 Linking periodontitis with 20 cancers, emphasis on oropharyngeal cancer: a Mendelian randomization analysis DOI:10.1038/s41598-024-63447-4 | 2024 | this review only | not stated | not extracted yet |
| Yan Gao et al.,2024 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Yang R 2024 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Yangyang Pi et al.,2024 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Yi-Qian Sun et al.,2020 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Yin KJ 2022 No Genetic Causal Association Between Periodontitis and Arthritis: A Bidirectional Two-Sample Mendelian Randomization Analysis DOI:10.3389/fimmu.2022.808832 | 2022 | this review only | not stated | not extracted yet |
| Yin KJ et al.,2022 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Yixuan Liu et al.,2024 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Zhang R 2024 Immune-mediated inflammatory diseases and periodontal disease: a bidirectional two-sample mendelian randomization study DOI:10.1186/s12865-024-00634-y | 2024 | this review only | not stated | not extracted yet |
| Zhang Z 2024 Biological aging mediates the association between periodontitis and cardiovascular disease: results from a national population study and… DOI:10.1186/s13148-024-01732-9 | 2024 | this review only | not stated | not extracted yet |
| Zhao Hu et al.,2024 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Zhao Y 2022 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Zhaoqi Zhang et al.,2024 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Zhengrui Li et al.,2024 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Zhongyuan Wang,2023 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
| Zijian Cheng et al.,2024 matched by author and year (probable) | NR | this review only | not stated | not extracted yet |
Review question
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | Populations in MR studies using genetic instruments for periodontitis | Mostly European-ancestry GWAS cohorts (78 MR studies; 34 in meta-analysis) |
| Intervention | Periodontitis as exposure (genetically predicted) | Genetically predicted periodontitis |
| Comparison | Not specified | Not specified |
| Outcomes | Systemic diseases as outcome | 19 diseases pooled: Alzheimer, Parkinson, stroke and subtypes, coronary atherosclerosis, depression, psoriasis, NAFLD, Sjogren, RA, diabetes, IBD, UC, Crohn, gastric cancer, hypothyroidism, hyperthyroidism |
| Study designs | Mendelian randomization studies (GWAS-based); meta-analysis only when at least three cohorts per disease | 78 MR studies in systematic review; 34 in meta-analysis |
| Timing | Not specified | Not specified |