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Poster Networking

Venous Thromboembolism

PB0940 - Polygenic risk score predictor of pulmonary embolism among those with a deep vein thrombosis: the INVENT Consortium

Monday, June 24, 2024
13:45 – 14:45 ICT
Room: Exhibition Hall
Background: Clots in the deep veins (DVT) that dislodge can travel to the pulmonary arteries producing pulmonary emboli (PE), which can be fatal.

Aims: Identifying polygenic risk associated with PE among those with a DVT may offer new insights into PE risk.

Methods: We tested a polygenic risk score (PRS) for association with PE among those with a DVT using GWAS summary data from studies with VTE events. In this case-only analysis, VTE cases were classified into: (a) DVT diagnosis with no evidence of PE within 2 weeks after the event; and (b) PE diagnosis regardless of concurrent DVT status in the previous 2 weeks. We used PRS-CSx to create a multi-ancestry PRS. From a large multi-ancestry meta-analysis of 26 studies, we split the data into a training dataset of approximately 90% of participants and reserved 10% for PRS testing. In the training sample we performed European and African ancestry meta-analyses and trained the PRS using PRS-CSx using matched ancestry 1000G reference panels. Scores were combined across ancestries to conduct an inverse-variance-weighted meta-analysis within the Gibbs sampler. The PRS was tested in the remaining 10% of the samples.

Results: Multi-ancestry weights for 1,277,694 variants were estimated from meta-analysis results of 44,361 DVT-only cases and 34,676 PE cases from 23 studies and used for the PRS, which were applied to the 5,019 DVT-only cases and 4,201 PE cases in 3 studies. A meta-analyzed multi-ancestry averaged PRS score was 0.028 (interquartile range: -0.375 - 0.626) in DVT-only cases and 0.045 (interquartile range: -0.35 - 0.65) in PE cases. Each unit increase in the PRS was associated with a beta of 0.047 (odds ratio of 1.05); p-value 0.035.

Conclusion(s): We detected a modest association between genome-wide genetic variation PRS and the risk of PE among those with a DVT. Ancestry-stratified analyses are underway.