A genome-wide scan of venous thrombosis found no new genes at all. That is the result worth reporting: the four loci already known account for what common variants explain, and one of them is your blood group.
A venous thromboembolism is a clot that forms where blood is moving slowly — usually a deep vein in the leg — and the danger is that a piece of it breaks off, travels to the lungs and blocks an artery there. Long flights, surgery, immobility, pregnancy, cancer and the contraceptive pill all raise the risk, and so does inheritance.
The inherited part of this is unusually well mapped, for a reason that is worth understanding.
A 2011 genome-wide scan tested 551,141 positions in 1,542 people with venous thrombosis against 1,110 controls. Twelve of them passed genome-wide significance.
All twelve fell in loci that were already known: ABO, F5, F11 and FGG. Not one new locus came out of the study.
Papers reporting nothing rarely get read, and this one is more informative than most that report something. It says the low-hanging fruit here was already picked — and it put a number on how much of the fruit that is. Common variants were estimated to explain about 35% of the genetic variance in who gets a clot.
They are not a random assortment of biology. Three are the clotting cascade itself and one is a sugar on the surface of a blood cell.
The study also argued, from haplotypes rather than single positions, for HIVEP1, PROCR and STAB2. rs867186 in PROCR — the endothelial protein C receptor — is on this page for that reason.
Blood group is not usually thought of as having anything to do with clotting. It does, through a protein you have probably never heard of.
Von Willebrand factor carries factor VIII around the bloodstream and helps platelets stick where they are needed. It is decorated with the same sugars that define the ABO blood groups, and those sugars change how quickly it is cleared. People with group O clear it faster, so they run lower levels of von Willebrand factor and factor VIII — and lower levels mean less clotting.
So ABO is in this list for a real mechanical reason, and the connection runs the other way from how people usually think about blood type. It is not that O is a lucky letter. It is that a sugar on a carrier protein changes how long that protein lasts. See ABO blood group.
Testing for thrombophilia is one of the more argued-about tests in medicine, and the argument is not about whether the variants are real. It is about what anyone does differently afterwards.
Most carriers of factor V Leiden never have a clot. Finding it in someone who has already had one rarely changes how long they are anticoagulated, because that decision turns on whether the clot was provoked and on bleeding risk. And the situations that matter most — surgery, immobility, pregnancy, oestrogen — are ones where prevention is offered on the clinical picture rather than on a genotype.
The clearest place a genotype does enter a conversation is oestrogen-containing contraception, where the two risks compound rather than add. That is covered on the combined hormonal contraceptives page.
If you have had a clot, or one runs in your family, this is a conversation with a haematologist. It is not a conversation with a raw data file.
Source. Germain et al. (PLoS One 2011) conducted a genome-wide association study of venous thrombosis based on 551,141 SNPs genotyped in 1,542 cases and 1,110 controls. Twelve SNPs reached the genome-wide significance level of 2.0 × 10⁻⁸ and encompassed four known VT-associated loci: ABO, F5, F11 and FGG. Haplotype analyses provided arguments in favour of HIVEP1, PROCR and STAB2, three loci then recently hypothesised to contribute. No novel VT-associated locus emerged. The authors estimated that common variants could explain approximately 35% of the genetic variance underlying susceptibility.
Positions listed here. rs6025 (F5, factor V Leiden), rs3756008 and rs4253399 (F11), rs7681423 (FGG), rs8176719 (ABO, the group O-determining frameshift) and rs867186 (PROCR). They were collected under several trait names — the ABO position under blood type and the FGG position under fibrinogen level — and are gathered here because this study is what connects them.
ABO mechanism. ABO antigens are carried on von Willebrand factor, and its glycosylation affects clearance rate. Group O individuals have lower plasma von Willebrand factor and consequently lower factor VIII, which is the accepted explanation for the reduced venous thrombosis risk associated with group O.
Clinical use. Thrombophilia testing is not recommended indiscriminately. Guidelines restrict it because a positive result seldom alters the duration of anticoagulation — which is determined chiefly by whether the event was provoked and by bleeding risk — and because prophylaxis in high-risk situations is offered on clinical grounds. Testing has a defined place in specific circumstances assessed by a haematologist, and consumer genotype files are not the instrument for it.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Venous Thromboembolism comes down to these specific, well-studied positions — not a diagnosis.
Because the absence is the finding. A scan of half a million positions in more than 2,600 people returned only loci that were already known, which says the common-variant contribution to this disease is concentrated in a few places rather than spread across hundreds — unusual, and useful to know.
It is associated with lower risk, and there is a mechanism rather than a coincidence: ABO antigens sit on von Willebrand factor and change how fast it is cleared, so group O runs lower von Willebrand factor and factor VIII. It shifts the odds. It is not protection you can rely on, and it changes nothing about the situational risks.
That is a question for a doctor, and the answer often turns out to be no. Thrombophilia testing is deliberately restricted because a positive result rarely changes how long someone is anticoagulated or whether they get prophylaxis before surgery — both are decided on the clinical picture. The one place it commonly enters a conversation is oestrogen-containing contraception.
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