HE INCIDENCE OF DEEP VEIN thrombosis (DVT) is 1 per 1000 person-years. 1 The10-yearrecurrence risk is 30%. 2 Deep vein thrombosis can lead to life-threatening pulmonary embolism. 3 Deep vein thrombosis is caused by acquired and genetic risk factors. Acquired risk factors include age, hospitalization, cancer, pregnancy, hormone therapy, and surgery. 2 Family and twin studies indicate that genetics ac-countsforabout60%oftheriskforDVT. 4,5 Deficiencies of natural anticoagulants antithrombin, protein C, and protein S are strong risk factors for DVT; however, the variantscausingthesedeficienciesarerare and explain only about 1% of all DVTs. 6 Two more common genetic variants, Factor V Leiden (FVL) and prothrombin G20210A, have been consistently found to be associated with DVT 7,8 but still only explain a fraction of the DVT events. 6 It has been suggested that 2 or more risk factors are needed for thrombosis. 6,9,10 The identification of additional common gene variants associated with DVT will improve the ability to predict risk for DVT and increase understanding of this disease. Therefore, we investigated whether any of 19 682 primarily missense single-nucleotide polymorphisms (SNPs) were associated with DVT in 3 large case-control studies. METHODS Study Populations and Data Collection The 3 studies (LETS, MEGA-1 and MEGA-2) in the present analysis are derived from 2 large population-based case-control studies: the Leiden Throm-bophilia Study (LETS) 11 and the Multiple Environmental and Genetic Assessment of Risk Factors for Venous Thrombosis (MEGA study). 12 These

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 thrombosisassociated 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,

In both the CARE and the WOSCOPS trials, carriers of the KIF6 719Arg allele had an increased risk of coronary events, and pravastatin treatment substantially reduced that risk.

Objective-We asked whether single nucleotide polymorphisms (SNPs) that had been nominally associated with cardiovascular disease in antecedent studies were also associated with cardiovascular disease in a population-based prospective study of 4522 individuals aged 65 or older. Methods and Results-Based on antecedent studies, we prespecified a risk allele and an inheritance model for each of 74SNPs. We then tested the association of these SNPs with myocardial infarction (MI) in the Cardiovascular Health Study (CHS). The prespecified risk alleles of 8 SNPs were nominally associated (1-sided PϽ0.05) with increased risk of MI in White CHS participants. The false discovery rate for these 8 was 0.43, suggesting that about 4 of these 8 are likely to be true positives. The 4 of these 8 SNPs that had the strongest evidence for association with cardiovascular disease before testing in CHS (association in 3 antecedent studies) were in KIF6 (CHS HRϭ1.29; 90%CI 1.1 to 1.52), VAMP8 (HRϭ1.2; 90%CI 1.02 to 1.41), TAS2R50 (HRϭ1.13; 90%CI 1 to 1.27), and LPA (HRϭ1.62; 90%CI 1.09 to 2.42). Key Words: coronary disease Ⅲ myocardial infarction Ⅲ genetics Ⅲ polymorphisms C ardiovascular disease is a complex disease with a genetic component, 1 and many genetic polymorphisms have been reported to be associated with cardiovascular disease. 2 However, to confirm these associations, they should be examined in other populations, ideally in population-based prospective studies that have sufficient power to detect the hypothesized associations. One such population-based prospective study is the Cardiovascular Health Study (CHS), a study of American men and women 65 years and older sponsored by the National Heart, Lung, and Blood Institute. 3,4 CHS offers several strengths, including a large population-based cohort, collection of baseline data for traditional risk factors, long follow-up, and central adjudication of cardiovascular events. Conclusions-AlthoughWe have been investigating the association between cardiovascular disease and single nucleotide polymorphisms (SNPs) using a panel of Ϸ12 000 mostly nonsynonymous SNPs. [5][6][7] The discovery studies for these investigations were conducted in case-control studies that included patients enrolled by investigators at the Cleveland Clinic Foundation (CCF) and the University of California, San Francisco (UCSF) [5][6][7] ; the association between 9 of these SNPs and cardiovascular disease in multiple discovery studies has been previously described. [5][6][7][8][9] We have used these 9 SNPs to build multiplex assays that are suitable for genotyping thousands of samples even when only a limited quantity of DNA is available for each sample. These multiplex assays also contain assays for 65 additional SNPs that were found to be associated with cardiovascular disease in one or more of the discovery studies (for these 65 SNPs, the results of the antecedent discovery studies are presented in the online supplement of this article, available online at http://atvb. ahajournals.org). We investigated wheth...