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Dan Roden
Faculty Member
Last active: 3/24/2020

STRATEGIES FOR EQUITABLE PHARMACOGENOMIC-GUIDED WARFARIN DOSING AMONG EUROPEAN AND AFRICAN AMERICAN INDIVIDUALS IN A CLINICAL POPULATION.

Wiley LK, Vanhouten JP, Samuels DC, Aldrich MC, Roden DM, Peterson JF, Denny JC
Pac Symp Biocomput. 2017 22: 545-556

PMID: 27897005 · PMCID: PMC5389380 · DOI:10.1142/9789813207813_0050

The blood thinner warfarin has a narrow therapeutic range and high inter- and intra-patient variability in therapeutic doses. Several studies have shown that pharmacogenomic variants help predict stable warfarin dosing. However, retrospective and randomized controlled trials that employ dosing algorithms incorporating pharmacogenomic variants under perform in African Americans. This study sought to determine if: 1) including additional variants associated with warfarin dose in African Americans, 2) predicting within single ancestry groups rather than a combined population, or 3) using percentage African ancestry rather than observed race, would improve warfarin dosing algorithms in African Americans. Using BioVU, the Vanderbilt University Medical Center biobank linked to electronic medical records, we compared 25 modeling strategies to existing algorithms using a cohort of 2,181 warfarin users (1,928 whites, 253 blacks). We found that approaches incorporating additional variants increased model accuracy, but not in clinically significant ways. Race stratification increased model fidelity for African Americans, but the improvement was small and not likely to be clinically significant. Use of percent African ancestry improved model fit in the context of race misclassification.

MeSH Terms (19)

Adult African Americans Aged Algorithms Anticoagulants Cohort Studies Computational Biology Cytochrome P-450 CYP2C9 European Continental Ancestry Group Female Gene Frequency Humans Male Middle Aged Models, Genetic Pharmacogenomic Variants Polymorphism, Single Nucleotide Vitamin K Epoxide Reductases Warfarin

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