As we age we acquire DNA changes (mutations) in our blood cells, a phenomenon called ‘clonal haematopoiesis’. In the vast majority of people these mutations do not cause any problems, but in a small number of people, if these mutations grow to high enough levels in the blood, they can increase the risk of developing a blood cancer and/ or cardiovascular disease (e.g. heart attack). Unfortunately, we are currently unable to reliably predict which mutations are associated with the highest risk of these conditions, or what specific factors drive or impede the growth of mutations in the blood over time. In order to understand this, we need to address the following questions:
What happens to the growth and survival of blood cells harbouring acquired mutations over time?
What effect do health and lifestyle factors have on the growth and survival of these blood cells?
How do changes in the immune system correlate with changes in health and lifestyle, and how does this affect the growth and survival of these blood cells?
How does the growth of mutations in the blood cells compare to the growth of mutations in other cell types in the same person, e.g. in the cells lining the mouth (‘buccal cells’)?
The LEGACY study aims to answer these questions by studying blood samples and mouth (‘buccal’) swab samples collected at regular intervals over a period of ~18 months (12 study visits), from the same individuals, together with concurrent information on their health and lifestyle, collected through questionnaires, NHS medical and health-related records and wearable devices (Fitbit). By then continuing to follow the health of participants long-term (through medical and other health-related records), we hope to assess whether particular changes detectable in the blood might be predictive of future illness.
Having to attend for regular blood tests limits the number of participants that can be recruited to longitudinal studies such as LEGACY, and so an additional aim of the study is to assess whether self-collected fingerprick and saliva samples can provide results that are of comparable accuracy to traditionally collected blood samples. If they can, then this will be invaluable for planning future studies with larger numbers of participants as it may allow participants to post self-collected samples from home, which will minimize the time and cost associated with frequent face-to-face study visits.