Three Genes for Blood Clots

Editor’s note: Pending an FDA decision, 23andMe no longer offers new customers access to health reports referred to in this post. Customers who purchased prior to November 22, 2013 will still be able to see their health reports, but those who purchased after that time will not. Those customers will have access to ancestry information as well as access to their uninterpreted raw data.

Numerous factors increase a person’s risk for developing blood clots in deep veins, a condition known medically as venous thromboembolism (VTE). VTE starts with the formation of a blood clot deep in the body, usually in the legs, and occasionally escalates into a more serious condition called “pulmonary embolism” if the clot breaks free and travels to the lungs. About one in 100 people with European ancestry will develop a blood clot in his or her lifetime and in nearly 25% percent of these cases the first sign will be sudden death.

Fracturing your hip or leg, having hip or knee replacement surgery, being immobilized like on a long flight, being pregnant, smoking, and taking oral birth control pills all increase risk for VTE to varying degrees. Genetics also plays a role and a new study by lead author John Heit from the Mayo Clinic suggests that variants of just three genes — F5, F2, and ABO — account for nearly all the possible genetic risk in people with European ancestry. These results imply that researchers are unlikely to discover new genetic factors that significantly impact VTE risk in the general population.

Two of the three major genes have especially large impacts on risk for VTE. The F5 gene encodes the factor V clotting factor, a protein that causes blood cells to stick together. People with one copy of the risky version of this gene (T at ) have a condition called “Factor V Leiden”, named after the city in the Netherlands where the role of this variant was first discovered, and are about five times more likely to develop VTE than people without the T version. The F2 gene encodes prothrombin, another clotting factor, and individuals with one risky version of this gene (A at i3002432) are nearly four times more likely to develop a blood clot compared to people without the A version. The risky versions of F5 and F2 are fairly rare in the general population.

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The ABO gene determines the common blood groups O, A, B and AB. It’s been shown that people with non-O blood types are at increased risk for VTE and a number of variants in or near the ABO gene have been associated with VTE risk. The study by Heit further confirms that the version of the ABO gene that makes someone have a non-O blood type also makes him or her about two times more likely to develop VTE.

(23andMe reports on a SNP in the ABO gene — — that is highly correlated with another SNP that defines the O blood group. People with at least one C at typically have a non-O blood type and are at increased risk for VTE.)

In addition to showing that versions of F5, F2 and ABO account for most risk in people with European ancestry, the study also suggested that a variant of the SELP gene further increases a person’s risk for VTE but only if he or she also inherited the risky version of F5 from the same parent. The SELP gene encodes a protein called P-Selectin and it’s already known that increased levels of P-Selectin are linked to VTE. But since less than 5% of the population even has the risky version of F5, this new finding only explains risk for a small number of people.

23andMe updated it’s VTE Established Research report in March of 2012 and currently reports on variants of the F5, F2, and ABO genes. Our report is thus very comprehensive for people with European ancestry. For reasons that are still unclear, VTE is much more common in people with European and African-American ancestry and less prevalent in Asian and Latino populations. More research is needed to define the genetic risk factors in non-European populations.