Neighborhood Deprivation and Polygenic Contribution to Acute Ischemic Stroke: Results from the All of Us Research Program (S49.007)

Abstract

<h3>Objective:</h3> We hypothesize that neighborhood deprivation, a geographic metric that captures several social determinants of health, modifies the effect of genetic variation on risk of acute ischemic stroke (AIS). <h3>Background:</h3> The interaction between social determinants of health and genetic risk factors in their association with AIS is poorly understood. <h3>Design/Methods:</h3> We ran a cross-sectional study in <i>All of Us</i>, a large population study that aims to enroll one million Americans. We ascertained AIS cases using Observational Medical Outcomes Partnership codes. We evaluated neighborhood deprivation using the deprivation index, an aggregate variable derived from six American Community Survey metrics divided into tertiles. We modeled the polygenic contribution to AIS through a polygenic risk score that included 530 known genetic risk variants for cardiometabolic risk factors. We used multivariable logistic regression to model AIS likelihood as a function of neighborhood deprivation and polygenic risk, using product terms to test for interaction, and adjusting for age, sex, and ethnicity. <h3>Results:</h3> Of the 372,397 participants currently enrolled in <i>All of Us</i>, 147,492 had available genetic and deprivation index data; of these, 3,201 (2.2%) had strokes. Both neighborhood deprivation and the polygenic risk score were independently associated with AIS (both p&lt;0.05). We found a significant interaction between neighborhood deprivation and polygenic risk (interaction p=0.02): the polygenic risk score was significantly associated with the likelihood of AIS in the least deprived areas (OR 1.08, 95%CI 1.02–1.15; p=0.01) but was not associated with AIS in moderately and highly deprived areas (both p&gt;0.05). <h3>Conclusions:</h3> Among study participants enrolled in All of Us, those living in areas of low neighborhood deprivation were more susceptible to the effects of polygenic variation. It is possible that social determinants of health associated with a higher likelihood of AIS dilute the contribution of genetic risk factors. <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. Acosta has nothing to disclose. Dr. Renedo 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.