Genetically proxied IL-6 signaling downregulation via IL6 perturbation was associated with lower risk of all outcomes (OR for CAD per 24% decrease in CRP of 0.87, 95% CI 0.76 to 0.997; OR for PAD of 0.67, 95% CI 0.48 to 0.94 and OR for IS of 0.78, 95% CI 0.62 to 0.98; Extended Data Fig. 6 and Supplementary Table 12). The gene discussed is CRP; the disease is peripheral arterial disease.