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

Ahmad, Abrar LU orcid ; Sundquist, Kristina LU ; Palmér, Karolina LU ; Svensson, Peter J. LU ; Sundquist, Jan LU and Memon, Ashfaque A. LU orcid (2019) In Journal of Thrombosis and Thrombolysis 47(2). p.216-226
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... (More)

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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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cox regression analyses, Genetic variants, Multiple SNPs model, Recurrent VTE
in
Journal of Thrombosis and Thrombolysis
volume
47
issue
2
pages
216 - 226
publisher
Springer
external identifiers
  • scopus:85055695423
  • pmid:30368761
ISSN
0929-5305
DOI
10.1007/s11239-018-1762-7
project
Identification of diagnostic and prognostic biomarkers of venous thromboembolism and its recurrence
Genetic risk factor of venous thromboembolism and its recurrence
language
English
LU publication?
yes
id
0c6b1b76-d21f-4f6c-95d0-f2506231c039
date added to LUP
2018-11-20 08:24:17
date last changed
2025-05-29 14:48:50
@article{0c6b1b76-d21f-4f6c-95d0-f2506231c039,
  abstract     = {{<p>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.</p>}},
  author       = {{Ahmad, Abrar and Sundquist, Kristina and Palmér, Karolina and Svensson, Peter J. and Sundquist, Jan and Memon, Ashfaque A.}},
  issn         = {{0929-5305}},
  keywords     = {{Cox regression analyses; Genetic variants; Multiple SNPs model; Recurrent VTE}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{216--226}},
  publisher    = {{Springer}},
  series       = {{Journal of Thrombosis and Thrombolysis}},
  title        = {{Risk prediction of recurrent venous thromboembolism : a multiple genetic risk model}},
  url          = {{http://dx.doi.org/10.1007/s11239-018-1762-7}},
  doi          = {{10.1007/s11239-018-1762-7}},
  volume       = {{47}},
  year         = {{2019}},
}