Periodontitis and Stroke: A Mendelian Randomization Study

Background And Purpose: Periodontitis has been implicated in the incidence of ischemic stroke. However, the generalizability of results to individuals with different subtypes of periodontitis is unknown. We aimed to investigate the causal relationship of chronic periodontitis (CP) and aggressive periodontitis (AgP) with ischemic stroke and its subtypes in the Mendelian randomization framework.

Methods: The genetic proxies of CP were derived from large-scale summary statistics from the UK Biobank datasets (950 cases and 455,398 controls). The genetic associations of AgP were selected from another large genome-wide association study of European ancestry (851 cases and 6836 controls). The instruments of ischemic stroke (34,217 cases and 406,111 controls) and its subtypes were selected from the MEGASTROKE consortium of European ancestry. The inverse variant weighted method was performed to determine the causal inference and a comprehensive set of sensitivity analyses to test the robustness of the results.

Results: In population-wide genetic analysis, there was no association of genetically predicted AgP (odds ratio [OR], 0.982; 95% confidence interval [CI], 0.956-1.009; p = .197) with ischemic stroke or its subtypes. For patients with CP, there was also no significant causal inference on ischemic stroke (OR, 1.017; 95% CI, 0.992-1.043; p = .184). However, regarding the stroke subtypes, the genetic analysis provided evidence of a causal relationship of CP with cardioembolic stroke (OR, 1.052; 95% CI, 1.002-1.104; p = .042), but not with large artery atherosclerosis (OR, 1.005; 95% CI, 0.944-1.069; p = .875) or small vessel occlusion (OR, 1.039; 95% CI, 0.981-1.101; p = .193).

Conclusion: This study suggested that there was a potential causal effect of CP on cardioembolic stroke.