Genetically determined ICAM-4 was positively associated with the risk of ischemic stroke in the sensitivity analyses with the penalized IVW method (OR per SD increase:1.04; 95% CI:1.01–1.07; P = 0.006), maximum likelihood method (OR per SD increase: 1.04; 95% CI:1.01–1.07; P = 0.003), and MR-RAPS method (OR per SD increase: 1.04; 95% CI:1.01–1.07; P = 0.003). The gene discussed is ICAM4; the disease is ischemic stroke.