What VKORC1 rs9923231 Means in My 23andMe Raw Data

VKORC1 rs9923231 is the main genetic marker in consumer DNA files for warfarin sensitivity. If your 23andMe raw data says AA at rs9923231, you are likely to need a lower warfarin dose than the population average. If it says GG, you are likely to need a higher dose. AG sits in the middle. This is a starting range, not a prescription.

What does VKORC1 mean in my 23andMe raw data?

VKORC1 is the gene for vitamin K epoxide reductase, the enzyme that warfarin blocks. rs9923231 is a single nucleotide change in the promoter of this gene, usually written as VKORC1 -1639G>A. In a raw file you will see rs9923231 on chromosome 16 with one of two alleles, A or G. The A allele is the lower-dose allele, the same one people mean by -1639A.

The practical parts:

• AA means lower VKORC1 enzyme expression. Warfarin hits harder.
• AG means intermediate expression and intermediate sensitivity.
• GG means higher expression, so the same dose is less effective.

For many adults, the eventual maintenance dose differs by roughly 2 to 3 mg per day between AA and GG. A person with AA often stabilises near the low end of the usual range, and a person with GG near the high end.

The mechanism: why a promoter change moves the dose

Warfarin works by reducing VKORC1 activity. That reduces vitamin K recycling, which reduces activation of clotting factors II, VII, IX and X. The dose is adjusted using INR, a blood test that measures how long clotting takes.

rs9923231 sits in the promoter region, the part of the gene that controls how much enzyme is made. The A allele reduces transcription of VKORC1. Less enzyme means the same amount of warfarin produces a larger anticoagulant effect. The G allele keeps transcription higher, so more enzyme is present and more warfarin is needed to get the same INR change.

This is why the genotype matters before any dose is chosen. It is also why it is not the whole story.

The VKORC1 result tells you which side of the warfarin dose range you are likely to start on. It does not tell you the dose itself.

How common is the lower-dose allele?

Frequencies vary by ancestry more than most drug response genes.

In populations with mostly European ancestry, the A allele is common but not dominant, so AA, AG and GG all appear regularly. In many East Asian populations, the lower-dose A allele is the majority variant, which is one reason standard warfarin doses in those populations often run lower. In populations with mostly African ancestry, the A allele is less common.

Does my VKORC1 result tell me my warfarin dose?

No. A raw DNA result gives you a direction, not a number.

Warfarin dosing uses INR measurements, age, weight, diet, interacting drugs and another gene called CYP2C9. CYP2C9 controls how fast warfarin is cleared. A person with VKORC1 AA but a CYP2C9 genotype that clears warfarin quickly may need a different dose than VKORC1 AA alone would suggest. Vitamin K intake, antibiotics, amiodarone, thyroid function and liver function all move the dose too.

The common mistake is treating VKORC1 as the dose. Dosing algorithms use it as one weighted variable among several. The INR is the actual feedback signal.

When the simple answer does not hold

The pattern is strong, but it thins at the edges. Some people with AA genotype need average or high doses because of diet or interacting drugs. Some people with GG need low doses. The variant explains about a quarter to a third of the variability in warfarin dose, which is a lot for one marker but leaves most of the difference unexplained. The exact percentage varies between studies.

The result also applies less cleanly to people with rare VKORC1 variants not captured by a typical 23andMe chip. Consumer chips interrogate specific positions. They do not sequence the whole gene.

If your actual INR and dosing history disagree with a genotype-based prediction, trust the INR and the clinical picture.

Where to see this in your own file

healthosx.com/dna

The download steps for 23andMe, on the page itself.

healthosx.com/dna

The short version: what is worth acting on, first.

If you already have a 23andMe, AncestryDNA, MyHeritage or whole-genome VCF file, the free DNA tool at https://healthosx.com/dna reads it in the browser and reports VKORC1 alongside CYP2C9 and other medication response markers. The file does not leave your device for the trait report. The DNA story needs no account; the full report opens in the HealthOS app after a 6-digit email code.