Finally, we further investigated the causal effect of PAI‐1 on known cardiovascular risk factors, including metabolic risk factors (ie, type 2 diabetes mellitus, body mass index [BMI], waist‐hip ratio, fasting blood glucose, insulin and lipids, and blood pressure) and subclinical atherosclerosis measures (ie, carotid intima‐media thickness, carotid plaque volume, and coronary artery calcification). This evidence concerns the gene SERPINE1 and type 2 diabetes mellitus.