Genetic Factors Influencing Warfarin Dose
Author Information
Author(s): Takeuchi Fumihiko, McGinnis Ralph, Bourgeois Stephane, Barnes Chris, Eriksson Niclas, Soranzo Nicole, Whittaker Pamela, Ranganath Venkatesh, Kumanduri Vasudev, McLaren William, Holm Lennart, Lindh Jonatan, Rane Anders, Wadelius Mia, Deloukas Panos
Primary Institution: Wellcome Trust Sanger Institute
Hypothesis
Can genetic variations predict the required dose of warfarin for patients?
Conclusion
The study confirms that VKORC1, CYP2C9, and CYP4F2 are significant genetic determinants of warfarin dose.
Supporting Evidence
- VKORC1 and CYP2C9 explain approximately 40% of the variability in warfarin dose.
- The study identified a new gene, CYP4F2, which contributes an additional 1%–2% to dose variability.
- Multivariate regression analysis was more effective in detecting weak genetic effects than univariate analysis.
Takeaway
Some people need more or less warfarin medicine because of their genes, and this study found three important genes that help doctors figure out the right dose.
Methodology
The study used a genome-wide association study (GWAS) design to analyze SNPs in 1,053 Swedish patients.
Limitations
The study may not have detected rare genetic variants that could influence warfarin dose.
Participant Demographics
1,053 Swedish patients
Statistical Information
P-Value
p<8.3×10−10
Statistical Significance
p<1.5×10−7
Digital Object Identifier (DOI)
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