Abstract
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.
Highlights
Genome-wide association studies (GWAS) have identified more than 20 loci that affect the risk of Alzheimer’s disease (AD) [1,2,3]
We did not find convincing evidence to support periodontitis being a causal factor for the development of AD
There was limited evidence to suggest genetic liability to AD being associated with the risk of periodontitis
Summary
Genome-wide association studies (GWAS) have identified more than 20 loci that affect the risk of Alzheimer’s disease (AD) [1,2,3]. It remains elusive which environmental factors increase the risk of late onset AD. Genetic variants used as instrumental variables in an MR study may be used to infer causal effect of the exposure if they satisfy three fundamental assumptions: 1) strongly associated with the exposure; 2) independent of confounding factors of the observational association; and 3) associated with the outcome only via the exposure (no horizontal pleiotropy) [10, 11]. We aimed to investigate the potential causal relationship between chronic periodontitis and AD in the population of European ancestry using a bidirectional two-sample MR method
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