Predicting venous thrombosis in women using a combination of genetic markers and clinical risk factors. (12th January 2015)

• Record Type: Journal Article
• Authors: Bruzelius, M.; Bottai, M.; Sabater‐Lleal, M.; Strawbridge, R. J.; Bergendal, A.; Silveira, A.; Sundström, A.; Kieler, H.; Hamsten, A.; Odeberg, J.
• Is Part Of: Journal of thrombosis and haemostasis. Volume 13:Number 2(2015:Feb.)
• Page Start: 219
• Page End: 227
• Publication Date: 2015-01-12
• Subjects: Thrombosis -- Periodicals; Hemostasis -- Periodicals; Blood coagulation disorders -- Periodicals; 616.1
• DOI: 10.1111/jth.12808
• Languages: English
• ISSNs: 1538-7933

Abstract

<abstract abstract-type="main" id="jth12808-abs-0001"> <title>Summary</title> <sec id="jth12808-sec-0001" sec-type="section"> <title>Background</title> <p>Family history of venous thromboembolism (VTE) has been suggested to be more useful in risk assessment than thrombophilia testing.</p> </sec> <sec id="jth12808-sec-0002" sec-type="section"> <title>Objectives</title> <p>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.</p> </sec> <sec id="jth12808-sec-0003" sec-type="section"> <title>Patients/Method</title> <p>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).</p> </sec> <sec id="jth12808-sec-0004" sec-type="section"> <title>Results</title> <p>Seven SNPs (<italic>F5</italic> rs6025, <italic>F2</italic> rs1799963, <italic>ABO</italic> rs514659, <italic>FGG</italic> rs2066865, <italic>F11</italic> rs2289252, <italic>PROC</italic> rs1799810 and <italic>KNG1</italic> 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.</p> </sec> <sec id="jth12808-sec-0005" sec-type="section"> <title>Conclusion</title> <p>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.</p> </sec> </abstract>