Abstract: Disclosed are methods of treating venous thromboembolism (VTE) in a subject, the method comprising administering a venous thrombus size lowering therapy to the subject, wherein the venous thrombus size lowering therapy is a plasminogen activator inhibitor 1 (PAI-1) inhibitor. Disclosed are methods of diagnosing and VTE, the method comprising diagnosing the subject as being at greater risk of developing VTE; and administering a venous thrombus size lowering therapy to the subject, wherein the venous thrombus size lowering therapy is a PAI-1 inhibitor. Disclosed are methods of determining a PRS for developing VTE in a subject comprising identifying the presence of one or more of the 297 SNPs identified in FIG. 19 are present in a biological sample from the subject; and calculating the PRS by summing the weighted risk score associated with each SNP identified.