Journal Article

Causal association between periodontitis and systemic diseases: a systematic review and meta-analysis of mendelian randomization studies

Chang, Xiaochi, Zhang, Churen, Shu, Chang, Zhao, Yanghao, Lin, Cheng, Zhang, Jie, Hou, Jianxia

2026

Overview

Background Periodontitis has increasingly been recognized for its impact on systemic health. Mendelian Randomization (MR), an emerging causal inference method, effectively overcomes confounding biases in observational studies. To systematically evaluate the causal relationship between periodontitis and various systemic diseases through a meta-analysis of mendelian randomization studies. Methods The China National Knowledge Infrastructure, WanFang data, PubMed, Web of Science and Science Direct were searched for mendelian randomization studies on periodontitis in relation to systemic disorders. Meta-analysis was performed on data gathered using the inverse-variance weighted and mendelian randomization-Egger methods. Results A total of 610 records was screened. The systematic review included 78 mendelian randomization experiments, while the meta-analysis included 34. There was strong evidence linking periodontitis to an increased risk of cardioembolic stroke and depression. However, the data showed that periodontitis had no substantial causal association with Alzheimer’s disease, Parkinson’s disease, coronary atherosclerosis, rheumatoid arthritis, hypothyroidism, hyperthyroidism, gastric cancer, psoriasis, Sjögren’s syndrome, or inflammatory bowel disease. Conclusions The evidence from mendelian randomization studies suggests that periodontitis plays a causal role in in cardioembolic stroke and depression. However, the rest of the findings differ from those of earlier observational research. As a result, future research should focus on resolving these constraints using bigger, more diverse populations and investigating the molecular mechanisms behind the observed relationships. Trial registration The PROSPERO database lists this meta-analysis under the registration number CRD42024581585.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Accuracy / Alzheimer's disease / Analysis / Arteriosclerosis / Arthritis / Asymmetry / Atherosclerosis / Bias / Care and treatment / Causal inference / Chronic obstructive pulmonary disease / Confounding (Statistics) / Control / Dentistry / Depression - etiology / Development and progression / Diagnosis / Epidemiology / Gastric cancer / Genetic aspects / Genetics / Genomes / Gum disease / Humans / Hyperthyroidism / Hypothyroidism / Identification and classification / Inflammatory bowel diseases / Information management / Mediation / Medicine / Mendelian randomization / Mendelian Randomization Analysis / Meta-Analysis / Microbial mats / Molecular modelling / Neurodegenerative diseases / Observational studies / Oral and Maxillofacial Surgery / Parkinson's disease / Periodontitis / Periodontitis - complications / Psoriasis / Rheumatoid arthritis / Rheumatoid factor / Sensitivity analysis / Sjogren's syndrome / Stroke - etiology / Systematic Review / Systemic diseases / Type 2 diabetes