Genetic susceptibility to T2DM and TG were positively associated with any ischemic stroke (OR = 1.048; 95%CI: 1.005, 1.091; p = 0.030) and small-vessel stroke (OR = 1.182; 95%CI: 1.035, 1.329; p = 0.026), explaining 35.7 and 22.8% of the total effect of SHBG levels on any ischemic stroke and small-vessel stroke, respectively. This evidence concerns the gene SHBG and small vessel stroke.