The Role of Socioeconomic Status in the Association between Genetic Predisposition and Cardiovascular Events: A UK...

Polygenic risk scores (PRS) summarize genetic variants associated with cardiovascular disease (CVD) risk. Socioeconomic status (SES) impacts CVD risk, but whether SES modifies genetic risk remains unclear. We investigated total and direct effects of the PRS for CVD on CVD events while accounting for SES and traditional risk factors. We followed UK Biobank participants recruited from 2006 to 2010 through 2022 with available PRS for CVD, SES (deprivation index, income, education), and cardiovascular risk factor data (diet, physical activity, smoking, sleep, body mass index, cholesterol, hbA1c, blood pressure). The primary outcome was first incident CVD event (myocardial infarction, heart failure, stroke, or CVD death). Competing-risk models were used to estimate total and direct effects of the PRS on CVD events after adjustment for age, sex, SES, and CVD risk factors. We additionally tested for interactions. Among 36,244 participants (mean age 55.3 ± 8.2 years; 53.6% female) with complete data, 1,900 (5.2%) experienced a CVD event. Each standard deviation increase in the PRS was associated with a higher risk of CVD events (HR 1.26, 95% CI 1.21 to 1.33), remaining significant after full adjustment (HR 1.23, 95% CI 1.18 to 1.29). Compared with the lowest-income group, participants with the highest income had 0.54 times the risk of a CVD event (HR 0.54, 95% CI 0.51 to 0.81). No significant interactions were observed. SES is independently associated with CVD events but does not modify genetic risk. CVD PRS remains directly associated with CVD after accounting for SES and traditional risk factors.