Abstract
Introduction: Socioeconomic status (SES) has a measurable and significant impact on cardiovascular disease incidence and outcomes. Study of its potential interactions with other known risk factors, such as genetics, remains an area for further research. Aim: To examine the interaction of polygenic risk for coronary artery disease (CAD) with socioeconomic status, as represented by income bracket. Methods: We utilized the NIH All of Us biobank, which integrates whole genome sequencing, electronic health record, and survey data. A previously-validated PRS for CAD (Inouye et al., 2018) was calculated for each patient. We subsetted the sample into high, medium, and low genetic risk groups per z-scores for the PRS: z-score >1, between 1 and -1, and <-1 respectively. Income information was derived from the survey data. Multivariable logistic regression was used to assess the performance of the PRS in this sample, with outcome defined as presence of CAD. The model was adjusted for PRS, age, gender, and the first 4 principal components of ancestry. Both income and the interaction of PRS by income were included as covariates. Results: In this sample of 97,405 individuals, this PRS is strongly associated with CAD prevalence: adjusted odds ratio for CAD per SD of the PRS was 1.96 (95% CI, 1.83-2.10). We then observed a differential effect of income on CAD. In the low and medium genetic risk groups, increasing income was associated with lower CAD prevalence. In the high genetic risk group, this protective effect was lost and CAD prevalence was overall similar across income brackets. Conclusions: These findings suggest a complex interaction between genetic risk of CAD and SES. High risk individuals may not derive the same benefit of improved SES and its material benefits. This unique subgroup will require uniquely targeted interventions, highlighting the need for deeper study of genetic risk in order to actualize the promises of precision medicine.
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