Bruzelius, M., Bottai, M., Sabater-Lleal, M., Strawbridge, R.J. , Bergendal, A., Silveira, A., Sundström, A., Kieler, H., Hamsten, A. and Odeberg, J. (2015) Predicting venous thrombosis in women using a combination of genetic markers and clinical risk factors. Journal of Thrombosis and Haemostasis, 13(2), pp. 219-227. (doi: 10.1111/jth.12808) (PMID:25472531)
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Abstract
Background: Family history of venous thromboembolism (VTE) has been suggested to be more useful in risk assessment than thrombophilia testing. Objectives: We investigated established genetic susceptibility variants for association with VTE and evaluated a genetic risk score in isolation and combined with known trigger factors, including family history of VTE. Patients/Method: A total of 18 single nucleotide polymorphisms (SNPs) selected from the literature were genotyped in 2835 women participating in a Swedish nationwide case-control study (the ThromboEmbolism Hormone Study [TEHS]). Association with VTE was assessed by odds ratios (ORs) with 95% confidence interval (CI) using logistic regression. Clinical and genetic predictors that contributed significantly to the fit of the logistic regression model were included in the prediction models. SNP-SNP interactions were investigated and incorporated into the models if found significant. Risk scores were evaluated by calculating the area under the receiver-operating characteristics curve (AUC). Results: Seven SNPs (F5 rs6025, F2 rs1799963, ABO rs514659, FGG rs2066865, F11 rs2289252, PROC rs1799810 and KNG1 rs710446) with four SNP-SNP interactions contributed to the genetic risk score for VTE, with an AUC of 0.66 (95% CI, 0.64–0.68). After adding clinical risk factors, which included family history of VTE, the AUC reached 0.84 (95% CI, 0.82–0.85). The goodness of fit of the genetic and combined scores improved when significant SNP-SNP interaction terms were included. Conclusion: Prediction of VTE in high-risk individuals was more accurate when a combination of clinical and genetic predictors with SNP-SNP interactions was included in a risk score.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Strawbridge, Dr Rona |
Authors: | Bruzelius, M., Bottai, M., Sabater-Lleal, M., Strawbridge, R.J., Bergendal, A., Silveira, A., Sundström, A., Kieler, H., Hamsten, A., and Odeberg, J. |
College/School: | College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Mental Health and Wellbeing |
Journal Name: | Journal of Thrombosis and Haemostasis |
Publisher: | Wiley |
ISSN: | 1538-7933 |
ISSN (Online): | 1538-7836 |
Published Online: | 04 December 2014 |
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