title: Multiple SNP testing improves risk prediction of first venous thrombosis.
abstract: There are no risk models available yet that accurately predict a person's risk for developing venous thrombosis. Our aim was therefore to explore whether inclusion of established thrombosis-associated single nucleotide polymorphisms (SNPs) in a venous thrombosis risk model improves the risk prediction. We calculated genetic risk scores by counting risk-increasing alleles from 31 venous thrombosis-associated SNPs for subjects of a large case-control study, including 2712 patients and 4634 controls (Multiple Environmental and Genetic Assessment). Genetic risk scores based on all 31 SNPs or on the 5 most strongly associated SNPs performed similarly (areas under receiver-operating characteristic curves [AUCs] of 0.70 and 0.69, respectively). For the 5-SNP risk score, the odds ratios for venous thrombosis ranged from 0.37 (95% confidence interval [CI], 0.25-0.53) for persons with 0 risk alleles to 7.48 (95% CI, 4.49-12.46) for persons with more than or equal to 6 risk alleles. The AUC of a risk model based on known nongenetic risk factors was 0.77 (95% CI, 0.76-0.78). Combining the nongenetic and genetic risk models improved the AUC to 0.82 (95% CI, 0.81-0.83), indicating good diagnostic accuracy. To become clinically useful, subgroups of high-risk persons must be identified in whom genetic profiling will also be cost-effective.
authors.affiliation: Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Hugoline G
authors.initials: HG
authors.lastname: de Haan
authors.forename: Irene D
authors.initials: ID
authors.lastname: Bezemer
authors.forename: Carine J M
authors.initials: CJ
authors.lastname: Doggen
authors.forename: Saskia
authors.initials: S
authors.lastname: Le Cessie
authors.forename: Pieter H
authors.initials: PH
authors.lastname: Reitsma
authors.forename: Andre R
authors.initials: AR
authors.lastname: Arellano
authors.forename: Carmen H
authors.initials: CH
authors.lastname: Tong
authors.forename: James J
authors.initials: JJ
authors.lastname: Devlin
authors.forename: Lance A
authors.initials: LA
authors.lastname: Bare
authors.forename: Frits R
authors.initials: FR
authors.lastname: Rosendaal
authors.forename: Carla Y
authors.initials: CY
authors.lastname: Vossen
mesh_terms: D003362:Cost-Benefit Analysis; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics; D005820:Genetic Testing / Q000191:economics / Q000379:methods* / Q000592:standards; D006801:Humans; D008297:Male; D008957:Models, Genetic; D015233:Models, Statistical; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011237:Predictive Value of Tests; D012372:ROC Curve; D015203:Reproducibility of Results; D012307:Risk Factors; D020246:Venous Thrombosis / Q000175:diagnosis* / Q000235:genetics*