Objective:

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).

Background:

The interaction between social determinants of health and genetic risk factors in their association with AIS is poorly understood. 

Design/Methods:

We ran a cross-sectional study in All of Us, 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. 

Results:

Of the 372,397 participants currently enrolled in All of Us, 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<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>0.05). 

Conclusions:

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.