Exploiting Common Genetic Variation to Make Anticoagulation Safer

Within the past 2 years, genomewide association studies have identified nearly 200 new chromosomal regions at which variation in DNA sequence influences risk of common human diseases as well as traits such as height and eye color. The success of the genomewide association study method, particularly given the limited success of previous approaches to find these “culprit” loci, has heightened optimism for the development of so-called personalized medicine. Perhaps more than any area, the field of anticoagulation and making it safer has raised hopes for using genetic information to improve individual patient outcomes. Discoveries, before the genomewide association study era, that common DNA sequence variants in CYP2C9 and VKORC1 play a substantial role in determining an individual’s warfarin dose requirement, led to an update of the US Food and Drug Administration label for Coumadin/warfarin suggesting that clinicians consider genetic testing before initiating warfarin.1 Although these discoveries represent a crucial first step toward the application of genetic information to make anticoagulation safer, it is clear that identifying an individual patient’s risk for hemorrhage on anticoagulation or thromboembolism in atrial fibrillation (and other diseases) will require many more genetic discoveries.