Environmental and Genetic Risk Factors Associated with Venous Thromboembolism

Abstract

Venous thromboembolism (VTE) includes deep vein thrombosis and pulmonary embolism; a combination of environmental and genetic risk factors contributes to VTE risk. Within environmental risk factors, some are provoking (e.g. cancer, surgery, trauma or fracture, immobilization, pregnancy and the postpartum period, long distance travel, hospitalization, catheterization, and acute infection) and others are non-provoking (e.g. age, sex, race/ethnicity, body mass index and obesity, oral contraceptive or hormone therapy use, corticosteroid use, statin use, diet, physical activity, sedentary time, and air pollution). Additionally, VTE has a strong genetic basis, with approximately 50–60% of the variance in VTE incidence attributed to genetic effects. Some genetic susceptibility variants that contribute to risk have been identified in candidate genes, mostly related to the clotting system and responsible for inherited hypercoagulable states (e.g., factor V Leiden, prothrombin, fibrinogen gamma, or blood group non-O). Other susceptibility single nucleotide polymorphisms have been identified from genome-wide association studies, such as the two new loci in TSPAN15 (rs78707713) and SCL44A2 (rs2288904) genes. Risk factors are not always associated with VTE in isolation, however, and an understanding of how environmental and genetic factors interact may provide insight into the pathophysiology of VTE, possibly identifying opportunities for targeted prevention and treatment.

Assessing the causal relationship between obesity and venous thromboembolism through a Mendelian Randomization study

“…In addition to its association with environmental risk factors like obesity, VTE has a strong genetic basis following a multifactorial inheritance model(Crous-Bou et al 2016). Most the identified genetic risk factors involve mutations in the clotting system, including: variants in factor V (e.g.…”

Interaction of a genetic risk score with physical activity, physical inactivity, and body mass index in relation to venous thromboembolism risk

“…Interactions between environmental risk factors and genetic risk scores have not been extensively studied with regards to VTE risk. In fact, only one previous study examined interactions of a genetic risk score for VTE with BMI and smoking (Crous-Bou, Harrington, & Kabrhel, 2016), though this study was smaller than our analysis and did not specifically assess additive interactions. Although we did not find evidence of interactions between the wGRS and physical activity or physical inactivity, the wGRS was positively associated with VTE risk and this was more pronounced among individuals with higher BMI.…”

“…Interactions between environmental risk factors and genetic risk scores have not been extensively studied with regards to VTE risk. In fact, only one previous study examined interactions of a genetic risk score for VTE with BMI and smoking (Crous-Bou, Harrington, & Kabrhel, 2016), though this study was smaller than our analysis and did not specifically assess additive interactions.…”

Association of prothrombin, FV Leiden and MTHFR gene polymorphisms in the Montenegrin patients with venous thromboembolism

“…Thrombophilia represents a group of inherited and acquired coagulation abnormalities associated with thrombosis. Although, thrombophilia itself is not a disease, it increases the risk of developing VTE in response to the provocation/perturbation by environmental factors 4,5 . Numerous acquired and hereditary risk factors are known to be responsible for the occurrence of VTE 5,6 .…”