Published in the journal Blood earlier this summer, the research identified variants in seven genes associated with myeloprofliferative neoplasms, or MPNs, a group of rare blood disorders that occur when bone marrow produces too many red or white blood cells, or platelets. Most forms of MPN are cancerous and all types are rare, affecting fewer than 100,000 people in the United States.
“This work represents a significant addition to our understanding of the genetic predispositions for classic myeloproliferative neoplasms,” said David Hinds, lead author of the study and 23andMe Principal Scientist and Statistical Geneticist. “And these insights were fueled by the participation of members of our MPN Research Community.”
Working with some of the leading MPN researchers in the world – Jason Gotlib and James L. Zehnder at Stanford, Ruben Mesa at the Mayo Clinic, and Marie Nguyen at the University of Michigan – 23andMe launched a community to study the genetics of MPN in 2011. The goal was to enroll 1,000 people with MPN into the research community, but within a year more than 1,700 people had joined and consented to participate in research. The study identified new genetic associations with MPNs that are inherited, germline mutations, which means that you were born with them. The study included data from more than 250,000 23andMe customers who consented to research, 726 of whom had some form of MPN and another 497 of whom are carriers of the V617F mutation (see below).
The scientists found variants on or near seven genes – TERT, SH2B3, TET2, ATM, CHEK2, PINT, and GFI1B – associated with MPN. These associations may also help in learning more about the underlying biology of the disease, for instance variants in the TERT gene are associated with certain kinds of tumors and increased red blood cell counts. The ATM gene is involved in controlling the rate at which cells grow and divide, and scientists believe that the TET2 gene is important in the production of blood cells from stem cells. The study also found that variants in those genes are also associated with the JAK2 V617F somatic mutation – a mutation that occurs after birth – that has previously been associated with developing MPNs.
Nearly all people with the polycythemia vera form of MPN have this mutation while many of those with the other two forms of MPN – essential thrombocythemia and myelofibrosis – also have it. What is also interesting about this study is that researchers were able to use inexpensive genotyping SNP arrays to detect not just inherited, germline mutations, but also the somatic V617F mutation. They were also able to detect the V617F mutation in individuals who had not reported having an MPN.
Both inherited and somatic mutations contribute to the development of MPN and something called “age-related clonal hematopoiesis,” which refers to a stem cell in the bone marrow making copy after copy of itself. Sometimes during the copying process the cell acquires a new somatic mutation. Researchers have found that in the development of different blood cells, these somatic mutations become more frequent as people age and can sometimes lead to blood cancer.
The researchers believe that custom SNP arrays, such as the one used by 23andMe, could also be used to look for additional somatic mutations linked to other blood disorders and cancers.
The study can be found in the journal Blood.