Harnessing Polygenic Risk Scores to Refine Venous Thromboembolism Risk Stratification

Area of Science:

• Genetics and genomics
• Cardiovascular medicine
• Pediatric medicine

Background:

• Venous thromboembolism (VTE) is a significant cause of illness across all age groups.
• The role of polygenic risk scores (PRS) in VTE susceptibility requires further investigation.
• This study assesses the independent contribution of PRS to VTE risk in adults and children.

Purpose of the Study:

• To evaluate the independent impact of a polygenic risk score (PRS) on venous thromboembolism (VTE) susceptibility.
• To compare the effectiveness of PRS in predicting VTE in adult and pediatric populations.
• To identify key clinical risk factors associated with VTE in both age groups.

Main Methods:

• A retrospective case-control study was conducted using two distinct cohorts (adults and children).
• Three VTE PRS models were evaluated, with a primary focus on a 293 single nucleotide polymorphism (SNP) PRS.
• Multivariable logistic regression analyses were performed to assess the association between risk factors and VTE in adults and children.

Main Results:

• A higher PRS was significantly associated with increased VTE odds in adults (OR=1.25 per SD increase).
• Key adult VTE risk factors included cancer (OR=2.43) and recent surgery (OR=2.16).
• The PRS also indicated increased VTE risk in children (OR=1.38), with central venous catheterization being the foremost risk factor (OR=5.65).

Conclusions:

• VTE in both adults and children is multifactorial, influenced by both clinical and genomic factors.
• Polygenic risk scores show promise as a valuable tool for VTE risk stratification.
• Integrating PRS with clinical risk factors may enhance the accuracy of VTE risk assessment.