Periodontitis causally affects the brain cortical structure: A Mendelian randomization study

Abstract Objective To estimate whether genetically proxied periodontitis causally impacts the brain cortical structure using Mendelian randomization (MR). Background Periodontitis is one of the most prevalent inflammatory conditions globally, and emerging evidence has indicated its influences on distal organs, including the brain, whose disorders are always accompanied by magnetic resonance imaging (MRI)‐identified brain cortical changes. However, to date, no available evidence has revealed the association between periodontitis and brain cortical structures. Methods The instrumental variables (IVs) were adopted from previous genome‐wide association study (GWAS) studies and meta‐analyses of GWAS studies of periodontitis from 1844 to 5266 cases and 8255 to 12 515 controls. IVs were linked to GWAS summary data of 51 665 patients from the ENIGMA Consortium, assessing the impacts of genetically proxied periodontitis on the surficial area (SA) or the cortical thickness (TH) of the global and 34 MRI‐identified functional regions of the brain. Inverse‐variance weighted was used as the primary estimate; the MR pleiotropy residual sum and outlier (MR‐PRESSO), the MR–Egger intercept test, and leave‐one‐out analyses were used to examine the potential horizontal pleiotropy. Results Genetically proxied periodontitis affects the SA of the medial orbitofrontal cortex, the lateral orbitofrontal cortex, the inferior temporal cortex, the entorhinal cortex, and the temporal pole, as well as the TH of the entorhinal. No pleiotropy was detected. Conclusions Periodontitis causally influences the brain cortical structures, implying the existence of a periodontal tissue–brain axis.