Related Experiment Video
Updated: Jun 4, 2026

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
The missing association: sequencing-based discovery of novel SNPs in VKORC1 and CYP2C9 that affect warfarin dose in
M A Perera1, E Gamazon, L H Cavallari
1Department of Medicine, Section of Genetic Medicine, University of Chicago, Chicago, Illinois, USA. mperera@bsd.uchicago.edu
Abstract:
It is well recognized that the genetic variants VKORC1-1639, CYP2C9*2, and CYP2C9*3 contribute to warfarin dose response. This has led to warfarin dosing algorithms that include these polymorphisms and explains between 47% and 56% of variability in dose in Caucasians. However, these polymorphisms explain significantly less of the variance in dose among African Americans. In order to identify novel variations that affect warfarin dose in African Americans, we used a targeted resequencing strategy that examined evolutionarily conserved sequences and regions of putative transcriptional binding. Through ethnicity-specific warfarin dose model building in 330 African Americans, we identified two novel genetic associations with higher warfarin dose, namely, VKORC1-8191 (rs61162043, P = 0.0041) and 18786 in CYP2C9 (rs7089580, P = 0.035). These novel finds are independent of the previous associations with these genes. Our regression model, encompassing both genetic and clinical variables, explained 40% of the variability in warfarin dose in African-American subjects, significantly more than any model thus far.
More Related Videos
Related Concept Videos
Genome-wide Association Studies-GWAS
GWAS does not require the identification of the target gene involved in...
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Single Nucleotide Polymorphisms-SNPs
Pharmacogenetics of Drug Metabolism: Overview
Principles of Pharmacogenetics: Types of Genetic Variants
Pharmacogenomics: Identification of New Drug Targets

