For 4 proteins with available cis instruments (IL18, TRAIL, TWEAK, and HGF), 2-sample mendelian randomization analysis suggested inverse associations of genetically elevated TWEAK with both CHD and ischemic stroke (HR, 0.93 [95% CI, 0.89-0.97] and 0.97 [95% CI, 0.93-0.99]; eFigure 9 and eTables 12 and 13 in the Supplement). This evidence concerns the gene TNFSF10 and ischemic stroke.