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Open Access 01-02-2019

Risk prediction of recurrent venous thromboembolism: a multiple genetic risk model

Authors: Abrar Ahmad, Kristina Sundquist, Karolina Palmér, Peter J. Svensson, Jan Sundquist, Ashfaque A. Memon

Published in: Journal of Thrombosis and Thrombolysis | Issue 2/2019

Abstract

A single genetic biomarker is unable to accurately predict the risk for venous thromboembolism (VTE) recurrence. We aimed to: (a) develop a multiple single nucleotide polymorphisms (SNPs) model to predict the risk of VTE recurrence and (b) validate a previously described genetic risk score (GRS) and compare its performance with the model developed in this study. Twenty-two SNPs, including established and putative SNPs associated with VTE risk, were genotyped in the Malmö thrombophilia study cohort (MATS; n = 1465, follow-up ~ 10 years) by using TaqMan PCR. Out of 22-SNPs, 12 had an association with the risk of VTE recurrence and were included for calculating GRSs. The risk of VTE recurrence was calculated by stratifying patients according to number of risk alleles. In 12-SNP GRS, patients with ≥ 7 risk alleles were associated with higher risk of VTE recurrence compared to patients having ≤ 6 risk alleles. In a simplified model (8-SNP GRS), the discriminative power of 8-SNP GRS was similar to that of 12-SNP GRS based on post-test probabilities (PP). Furthermore, 8-SNP GRS further improved the risk prediction of VTE recurrence in unprovoked VTE and male patients (PP% = 15.4 vs 8.3, 17.1 vs 7.2 and 19.0 vs 7.1 for high risk groups vs low risk groups in whole population, males and unprovoked VTE patients respectively). In addition, we also validated previously described 5-SNP GRS in our cohort and found that the 8-SNP GRS performed better than the 5-SNP GRS in terms of higher PP. Our results show that a multiple SNP GRS consisting of 8-SNPs may be an effective model for prediction of VTE recurrence, particularly in unprovoked VTE and male patients.

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Title: Risk prediction of recurrent venous thromboembolism: a multiple genetic risk model
Authors: Abrar Ahmad
Kristina Sundquist
Karolina Palmér
Peter J. Svensson
Jan Sundquist
Ashfaque A. Memon
Publication date: 01-02-2019
Publisher: Springer US
Published in: Journal of Thrombosis and Thrombolysis / Issue 2/2019
Print ISSN: 0929-5305
Electronic ISSN: 1573-742X
DOI: https://doi.org/10.1007/s11239-018-1762-7

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