What you carry at this position in your DNA and what research says about it.
Warfarin Sensitivity: 8/10 evidence, 19 publications.
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Sample genotype (not yours): C/C
Typical Warfarin Response
A typical response to warfarin is expected. There is no elevated sensitivity to the medication associated with this genotype.
What this genotype means: Typical warfarin response; Typical bone mineral density; Baseline vitamin K recycling efficiency.
Sample genotype (not yours): C/G
Moderate Warfarin Sensitivity
Intermediate sensitivity to warfarin: this genotype sits between the two homozygous patterns in how strongly the drug acts.
What this genotype means: Moderately greater warfarin sensitivity; Intermediate sensitivity to anticoagulants; Typical baseline health markers.
Sample genotype (not yours): G/G
High Warfarin Sensitivity
High sensitivity to warfarin: the drug produces a much stronger effect at a given amount. This genotype is also linked to higher circulating vitamin K1 levels.
What this genotype means: Significantly greater warfarin sensitivity; Highly sensitive to oral anticoagulants; Higher circulating vitamin K1 levels.
Gene function and biological role
Gene Function: The VKORC1 gene encodes vitamin K epoxide reductase complex subunit 1, a critical enzyme responsible for recycling oxidized vitamin K back into its active form [1]. This active vitamin K is a mandatory cofactor for the gamma-carboxylation of several clotting factors, making it indispensable for normal blood coagulation [1]. Because of its central role in the vitamin K cycle, VKORC1 is the primary molecular target of the widely prescribed anticoagulant medication warfarin [2]. Beyond blood clotting, VKORC1 activity also influences the activation of bone-related proteins like osteocalcin, which are essential for calcium binding and skeletal health.
Variant Impact: The rs8050894 variant is an intronic single nucleotide polymorphism located within the VKORC1 gene. This genetic change serves as a key tag marker for major VKORC1 haplotypes that regulate how much of the enzyme is produced in the liver [1]. The G allele is strongly associated with reduced VKORC1 gene expression, which decreases the overall amount of active enzyme available to recycle vitamin K [1]. Consequently, individuals carrying the G allele show greater sensitivity of warfarin to achieve therapeutic anticoagulation, as there is less target enzyme to inhibit [3]. This variant is in high linkage disequilibrium with other well-known functional polymorphisms, making it highly predictive of drug response across diverse ancestral populations [3].
Key Insight: This single genetic variant is one of the strongest predictors of how your body responds to the blood thinner warfarin, explaining why the drug's effect varies so widely between people.
Location: VKORC1. Chromosome 16 · 16p11.2 · 31.1 Mb
Estimated prevalence by population
Global 40.4%; European 37.7%; African 53.2%; East Asian 1.1%; South Asian 65.1%; Americas 32.6%; Ashkenazi 25.2%; Finnish 34.3%; Middle Eastern 18.8%; Amish 25.9%.
Estimated CC genotype frequency.
Global 44.1%; European 47.4%; African 39.5%; East Asian 18.9%; South Asian 31.2%; Americas 49.0%; Ashkenazi 50.0%; Finnish 48.5%; Middle Eastern 49.1%; Amish 50.0%.
Estimated CG genotype frequency.
Global 15.6%; European 14.9%; African 7.3%; East Asian 80.0%; South Asian 3.7%; Americas 18.4%; Ashkenazi 24.8%; Finnish 17.2%; Middle Eastern 32.1%; Amish 24.1%.
Estimated GG genotype frequency.
Showing effects for C/C genotype
Pharmacogenomics
Anticoagulant & Blood Thinner Response
Warfarin Dosage. Evidence: 8/10. Source: PMID 16270629. Typical Response.
Nutrition & Metabolism
Vitamin & Mineral Metabolism
Vitamin K Status. Evidence: 4/10. Source: PMID 19436136. Typical Levels.
Organ Systems
Bone, Joint & Connective Tissue Health
Bone Mineral Density. Evidence: 3/10. Source: PMID 21179439. Typical Density.
Cardiovascular & Metabolic
Obesity & Body Composition
Body Fat Distribution. Evidence: 6/10. Source: PMID 30664634. Slightly Higher Ratio.
Showing effects for C/G genotype
Warfarin Dosage. Evidence: 8/10. Source: PMID 16270629. Higher Sensitivity.
Bone Mineral Density. Evidence: 3/10. Source: PMID 21179439. Slightly Lower.
Body Fat Distribution. Evidence: 6/10. Source: PMID 30664634. Typical Ratio.
Showing effects for G/G genotype
Warfarin Dosage. Evidence: 8/10. Source: PMID 16270629. Much Higher Sensitivity.
Vitamin K Status. Evidence: 4/10. Source: PMID 19436136. Higher Vitamin K1.
Bone Mineral Density. Evidence: 3/10. Source: PMID 21179439. Lower Density.
Body Fat Distribution. Evidence: 6/10. Source: PMID 30664634. Slightly Lower Ratio.
What this genotype means for the people who carry it
Sample genotype: CC (Homozygous)
Having the C/C genotype means carrying two copies of the major allele, which is associated with normal or higher levels of VKORC1 expression in the liver [1]. Because there is an abundant amount of the target enzyme available, warfarin produces a comparatively weaker anticoagulant effect at a given amount [2]. This genotype is considered the baseline or wild-type response in many clinical dosing algorithms [2]. In terms of general health, this genotype is associated with typical bone mineral density and standard vitamin K recycling efficiency. It also correlates with a slightly higher ratio of upper-body fat distribution compared to G/G carriers, though the overall physiological impact of this metabolic association is very minor.
Typical warfarin response; Typical bone mineral density; Baseline vitamin K recycling efficiency.
Sample genotype: CG (Heterozygous)
Carrying one copy of the G allele reduces the overall expression of the VKORC1 enzyme in liver tissue [1]. With fewer target enzymes present, warfarin produces a stronger blood-thinning effect at a given amount than in the C/C genotype [2]. Studies place this heterozygous genotype at moderate sensitivity to the drug, between the two homozygous patterns [2]. Outside of medication response, this genotype is associated with typical vitamin K status and standard bone mineral density. It represents an intermediate genetic profile with no standalone health risks, making it primarily relevant to how researchers group warfarin response by genotype.
Moderately greater warfarin sensitivity; Intermediate sensitivity to anticoagulants; Typical baseline health markers.
Sample genotype: GG (Homozygous)
Carrying two copies of the G allele results in significantly reduced expression of the VKORC1 enzyme [1]. Because there is a very low concentration of the target enzyme, even small amounts of warfarin can cause a profound anticoagulant effect [2]. This is one of the strongest and most consistently replicated genetic signals in the published warfarin literature [2]. Interestingly, this genotype is also associated with significantly higher circulating levels of plasma phylloquinone (vitamin K1), suggesting a unique metabolic adaptation in vitamin K transport or utilization [3]. However, some studies have also noted a modest association between this genetic profile and slightly lower bone mineral density in specific populations, likely due to altered tissue-specific carboxylation of bone proteins [4].
Significantly greater warfarin sensitivity; Highly sensitive to oral anticoagulants; Higher circulating vitamin K1 levels.
Variants with shared genetic architecture
rs2359612 · VKORC1 Gene · Chr 16 · Cardiovascular Risk
rs2884737 · VKORC1 Gene · Chr 16 · Warfarin Sensitivity
rs61742245 · VKORC1 Gene · Chr 16 · Warfarin Resistance
Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose.
Content updated August 2026.
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