Genetic sensitivity to stress modifies the relationship between socioeconomic status and major adverse cardiovascular events

Abstract Background Lower socioeconomic status (SES) associates with major adverse cardiovascular events (MACE), in part through stress-related neural pathways that elicit inflammation. However, it is unknown whether genes that heighten stress sensitivity modify the association between lower SES and MACE. Purpose To assess whether genetic predisposition to stress sensitivity would modify the link between low SES and MACE Methods 13,154 participants (median age 60 yrs, 41% male) from the Mass General Brigham Biobank were studied. A polygenic risk score for neuroticism (nPRS) was used as a measure of genetic predisposition to stress sensitivity (GSS). Using home addresses, SES was evaluated as median income and area deprivation index (ADI). Stress-related neural activity (SNA) was assessed (N=978) using validated FDG PET/CT imaging methods. MACE, and cardiovascular disease (CVD) risk factors were evaluated. Mediation analyses were employed. Results Over median (IQR) 4.9 (4.1–5.9) years of follow-up, 1,030 (7.8%) individuals had MACE. Lower SES (as low income, or alternatively as high ADI) associated with incident MACE among individuals with higher GSS (nPRS ≥ median) but not lower GSS (Fig. 1A and 1B). Similarly, lower SES associated with SNA among individuals with higher but not lower GSS (Fig. 1C). SNA mediated the relationship between income and MACE (P<0.05**) among those with higher GSS. Conclusions Genetic predisposition to stress sensitivity appears to heighten CVD risk associated with lower SES. This relationship may result from differential activation of stress-related neural pathways. Funding Acknowledgement Type of funding sources: None.