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DALLAS -- Certain social determinants of health may dilute the contribution of genetics to acute ischemic stroke susceptibility in some people, according to a large-scale study.

Based on the NIH's All of Us program, an initiative to enroll 1 million people in a diverse health database for research, acute ischemic stroke risk correlated significantly with both community deprivation and personal genetic factors as indexed by the Deprivation Index and a polygenic risk score, respectively.

However, there was a significant interaction between genetic risk and neighborhood deprivation: only people in the lowest tertile of deprivation saw an effect of genetics on stroke risk (OR 1.08, 95% CI 1.02-1.15), whereas the intermediate and high deprivation groups did not see such genetic susceptibility play out in actual events (P=0.02 for interaction), reported Cyprien Rivier, MD, a postdoctoral researcher at Yale University School of Medicine in New Haven, Connecticut, during the American Stroke Association's International Stroke Conference.

As only residents of privileged areas "were more susceptible to the effects of polygenic variation on the risk of ischemic stroke," Rivier speculated "that in areas of high deprivation, the environmental risk factors become more important than genetic predisposition."

Randolph Marshall, MD, of Columbia University Irving Medical Center and New York-Presbyterian Hospital in New York City, called it a "reasonable hypothesis that the genetic component is overshadowed perhaps by the other factors related to neighborhood deprivation."

Yet epigenetics may also play a role in stroke risk, given that such gene activity can be explained by socially structured stressors, suggested Marshall, speaking at the audience Q&A.

Rivier agreed with Marshall's hypothesis and said that All of Us, which includes electronic health records, biospecimens, surveys, and wearables data, doesn't include the data for epigenetic analysis.

The present cross-sectional analysis included nearly 150,000 individuals, split evenly by tertiles of neighborhood deprivation.

The Deprivation Index used in the study -- based on the Census Bureau's American Community Survey -- quantifies a neighborhood's standard of living, health, education, economic security, housing quality, and neighborhood quality.

Meanwhile, genetic factors predisposing an individual to acute ischemic stroke were aggregated in a polygenic risk score that covers 530 variants associated with important stroke risk factors, namely blood pressure, cholesterol, glucose, BMI, diet, physical activity, and smoking. These seven domains come from the American Heart Association's old "Life's Simple 7" framework, recently replaced by "Life's Essential 8" to include sleep health.

Rivier reported that compared with residents of the most privileged neighborhoods, the most deprived individuals tended to be younger (49.3 vs 54.4 years for least deprived, P<0.001) and more likely Black (34.3% vs 6.9%, P<0.001) or Hispanic (27.1% vs 7.7%, P<0.001). They also had a higher polygenic risk score (0.11 vs -0.13, P<0.001).

The incidence of acute ischemic stroke was 1.5% in the most deprived group, significantly lower than the 2.0% for intermediate and low deprivation groups (P<0.001). However, Rivier said high deprivation actually corresponded with more strokes upon adjustment for age and other factors.

"It is important to note that our results are specific to this particular risk score and condition. We expect other combinations of genetic factors and environment to be evaluated," he cautioned.

During the session Q&A, another audience member asked if there is any implementation plan in place or next steps to put study findings into action.

Rivier acknowledged that his group does not have the expertise to implement this, but encouraged others to take this on.

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