In this, the first large, comprehensive, multiethnic prospective cohort study to quantify the risk reduction associated with the minor allele (G) of the FOXO3 longevity‐associated genotype, we demonstrated a large (10%) protective effect against all‐cause mortality and 26% for CHD mortality over 17 years of follow‐up. The gene discussed is FOXO3; the disease is coronary artery disorder.