Abstract 564: Influence of Coronary Artery Disease-Associated Genetic Variants on Risk of Venous Thromboembolism
Objective To determine whether genetic variation robustly associated with coronary artery disease (CAD) also influences risk of venous thromboembolism (VTE) in a well-defined, female case-control study (n=2753) from Sweden (the ThromboEmbolism Hormone Study (TEHS)).
Approach and Results Single nucleotide polymorphisms associated with CAD in genome-wide association studies were genotyped in TEHS. Association with VTE was assessed by logistic regression (Bonferroni-corrected p-values). A strong association was found between rs579459 in the ABO locus and VTE risk (p=3.8×1013). Adjustment for known VTE-associated variants within the ABO, F5, F2, F11 and FGG loci, along with age and body-mass index, identified a further suggestive association for rs1333049 in the ANRIL locus (p=0.003). However, replication analysis in 3 French cohorts (total n=5503) failed to confirm the ANRIL association with VTE, but indicated that the effect direction is consistent across cohorts. Furthermore, marked variation was found in minor allele and minor allele frequency of the ANRIL variant in a survey of studies conducted across Europe.
Conclusions CAD-associated genetic variants in the ABO and ANRIL loci appear to influence risk of VTE. Differences in cohort characteristics, including allele frequencies, may account for the failure to replicate the association with rs1333049 in the French cohorts.
- © 2013 by American Heart Association, Inc.