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Predicting venous thrombosis in women using a combination of genetic markers and clinical risk factors.

Authors: Bruzelius, M  Bottai, M  Sabater-Lleal, M  Strawbridge, RJ  Bergendal, A  Silveira, A  Sundstrom, A  Kieler, H  Hamsten, A  Odeberg, J 
Citation: Bruzelius M, etal., J Thromb Haemost. 2015 Feb;13(2):219-27. doi: 10.1111/jth.12808. Epub 2015 Jan 12.
Pubmed: (View Article at PubMed) PMID:25472531
DOI: Full-text: DOI:10.1111/jth.12808

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.

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CRRD Object Information
CRRD ID: 11059890
Created: 2016-04-18
Species: All species
Last Modified: 2016-04-18
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.