Joint Association of Polygenic Risk and Social Determinants of Health with Coronary Heart Disease in the United States.

Background: The joint effects of polygenic risk and social determinants of health (SDOH) on coronary heart disease (CHD) in the United States are unknown.

Methods: In 67,256 All of Us (AoU) participants with available SDOH data, we ascertained self-reported race/ethnicity and calculated a polygenic risk score for CHD (PRS ). We used 90 SDOH survey questions to develop an SDOH score for CHD (SDOH ). We assessed the distribution of SDOH across self-reported races and US states. We tested the joint association of SDOH and PRS with CHD in regression models that included clinical risk factors.

Results: SDOH was highest in self-reported black and Hispanic people. Self-reporting as black was associated with higher odds of CHD but not after adjustment for SDOH . Median SDOH values varied by US state and were associated with heart disease mortality. A 1-SD increase in SDOH was associated with CHD (OR=1.36; 95% CI, 1.29 to 1.46) and incident CHD (HR=1.73; 95% CI, 1.27 to 2.35) in models that included PRS and clinical risk factors. Among people in the top 20% of PRS , CHD prevalence was 4.8% and 7.8% in the bottom and top 20% of SDOH , respectively.

Conclusions: Increased odds of CHD in self-reported black people are likely due to higher SDOH burden. SDOH and PRS were independently associated with CHD in the US. Our findings emphasize the need to consider both PRS and SDOH for equitable disease risk assessment.