Variation in smoking and systolic blood pressure had the strongest causal life-shortening effects (5.3 and 5.2 years, respectively), followed by fasting insulin, body mass index and CAD, while years of education showed by far the most beneficial effect (4.7 years), when comparing the estimated effect of moving from the first to the third quartile of the phenotype distribution. The gene discussed is INS; the disease is coronary artery disorder.