Mediation of coronary heart disease risk by genetic, socio-environmental, and lifestyle factors across racial groups

We investigated the extent to which differences in coronary heart disease (CHD) risk between self-identified race/ethnicity (SIRE) groups are mediated by genetic, socio-environmental, and lifestyle factors. In UK Biobank, we estimated genetic susceptibility for CHD using a polygenic risk score (PRS CHD ) based on 1.7 million single-nucleotide variants (PGS Catalog identification: PGS000018), and socio-environmental-lifestyle risk for CHD using a polysocial risk score (PSS CHD ) based on 100 covariates. Using SIRE, participants were grouped as White or non-White (Asian/Asian British, Black/Black British, and Chinese). Incident CHD was defined as a composite of fatal and non-fatal myocardial infarction and coronary revascularization. Multivariable Cox regression and mediation analyses were performed. Of 382,475 participants (55.6±8.1 years, 57.5% female, 94.9% White, 1.7% Asian/Asian British, 1.6% Black/Black British, and 0.3% Chinese), 9,679 (2.5%) had an incident CHD event, during 10 years of follow-up. The adjusted hazard ratios (HR) and 95% confidence intervals (CIs) for a 1 SD increase in PSS CHD , and PRS CHD for CHD risk were 1.32 (1.30 to 1.35, P