Mixed evidence for the relationship between periodontitis and Alzheimer’s disease: A bidirectional Mendelian randomization study

Autoři: Yi-Qian Sun aff001;  Rebecca C. Richmond aff003;  Yue Chen aff004;  Xiao-Mei Mai aff005
Působiště autorů: Center for Oral Health Services and Research Mid-Norway (TkMidt), Trondheim, Norway aff001;  Department of Clinical and Molecular Medicine (IKOM), NTNU—Norwegian University of Science and Technology, Trondheim, Norway aff002;  School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom aff003;  School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, Canada aff004;  Department of Public Health and Nursing, NTNU—Norwegian University of Science and Technology, Trondheim, Norway aff005
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0228206


Recent experimental studies indicated that a periodontitis-causing bacterium might be a causal factor for Alzheimer’s disease (AD). We applied a two-sample Mendelian randomization (MR) approach to examine the potential causal relationship between chronic periodontitis and AD bidirectionally in the population of European ancestry. We used publicly available data of genome-wide association studies (GWAS) on periodontitis and AD. Five single-nucleotide polymorphisms (SNPs) were used as instrumental variables for periodontitis. For the MR analysis of periodontitis on risk of AD, the causal odds ratio (OR) and 95% confidence interval (CI) were derived from the GWAS of periodontitis (4,924 cases vs. 7,301 controls) and from the GWAS of AD (21,982 cases vs. 41,944 controls). Seven non-overlapping SNPs from another latest GWAS of periodontitis was used to validate the above association. Twenty SNPs were used as instrumental variables for AD. For the MR analysis of liability to AD on risk of periodontitis, the causal OR was derived from the GWAS of AD including 30,344 cases and 52,427 controls and from the GWAS of periodontitis consisted of 12,289 cases and 22,326 controls. We employed multiple methods of MR. Using the five SNPs as instruments of periodontitis, there was suggestive evidence of genetically predicted periodontitis being associated with a higher risk of AD (OR 1.10, 95% CI 1.02 to 1.19, P = 0.02). However, this association was not verified using the seven independent SNPs (OR 0.97, 95% CI 0.87 to 1.08, P = 0.59). There was no association of genetically predicted AD with the risk of periodontitis (OR 1.00, 95% CI 0.96 to 1.04, P = 0.85). In summary, we did not find convincing evidence to support periodontitis being a causal factor for the development of AD. There was also limited evidence to suggest genetic liability to AD being associated with the risk of periodontitis.

Klíčová slova:

Alzheimer's disease – Cognitive impairment – Europe – Genetics of disease – Genome-wide association studies – Instrumental variable analysis – Molecular genetics – Periodontitis


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