Genetic Analyses of Oral Health and Neuroimaging Markers of Brain Health in Persons without Stroke (S49.001)

Abstract

<h3>Objective:</h3> We hypothesize that genetically-determined poor oral health leads to worse neuroimaging brain health profiles in persons without stroke. <h3>Background:</h3> Oral health is a modifiable risk factor for stroke. However, the role of oral health on brain health among clinically asymptomatic persons remains understudied. <h3>Design/Methods:</h3> We conducted a two-sample Mendelian Randomization (MR) study. As instruments, we used 105 genetic variants known to be associated (p&lt;5×10⁻⁸) with a composite of caries, dentures and missing teeth in the Gene-Lifestyle Interactions in Dental Endpoints (GLIDE) Consortium. In stroke-free participants enrolled in the UK Biobank, we tested for associations between these genetic variants and white matter hyperintensity volume (natural log-transformed), fractional anisotropy and mean diffusivity. For the last two neuroimaging traits, we evaluated composite scores defined by the first principal component of measurements obtained across 48 brain regions. <h3>Results:</h3> Our primary analysis using the inverse variance-weighted MR method indicated that genetically-increased risk of poor oral health was associated with: (1) higher burden of silent cerebrovascular disease, as represented by a 30 % increase in white matter hyperintensities volumes (beta=0.30, SE=0.06 p-value=3×10⁻⁶), and (2) increased microstructural damage, as represented by a 43% change in composite FA scores (beta=0.43, SE=0.06; p=6×10⁻¹¹) and a 10% change in composite MD scores (beta=0.10, SE=0.03; p=0.005). Sensitivity analyses identified horizontal pleiotropy in our primary results, but an outlier-corrected analysis confirmed each of our findings (all p-values &lt;0.001). <h3>Conclusions:</h3> Among persons without stroke, genetically-determined poor oral health is associated with worse neuroimaging brain health profiles. Because gene-disease associations are immune to confounding, our results suggest that this association is causal. Early treatment of poor oral health may lead to significant brain health benefits, even in persons without stroke. <b>Disclosure:</b> Dr. Rivier has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Pyxis Partners. Dr. Renedo has nothing to disclose. Dr. De Havenon has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Integra. Dr. De Havenon has stock in Certus. The institution of Dr. De Havenon has received research support from NIH/NINDS. The institution of Dr. De Havenon has received research support from Regeneron Pharmaceuticals. The institution of Dr. De Havenon has received research support from AMAG Pharmaceuticals. The institution of Dr. De Havenon has received research support from AMGEN. Dr. De Havenon has received publishing royalties from a publication relating to health care. Sam Payabvash has nothing to disclose. Mr. Torres-Lopez has nothing to disclose. Thomas Gill has nothing to disclose. Dr. Sheth has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ceribell. Dr. Sheth has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Zoll. Dr. Sheth has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for NControl. Dr. Sheth has received stock or an ownership interest from Astrocyte. Dr. Sheth has received stock or an ownership interest from Alva. The institution of Dr. Sheth has received research support from Biogen. The institution of Dr. Sheth has received research support from Novartis. The institution of Dr. Sheth has received research support from Bard. The institution of Dr. Sheth has received research support from Hyperfine. Dr. Sheth has received intellectual property interests from a discovery or technology relating to health care. The institution of Dr. Falcone has received research support from NIH. The institution of Dr. Falcone has received research support from AHA.