As cells age they acquire mutations. Healthy individuals have been shown to carry acquired mutations. Commonly, these mutations will have no ill impact on the health of a given individual. In extreme cases these mutations may result in other mutations that ultimately produce a malignancy. However, there is a middle ground where individuals carry acquired mutations and do not develop cancer, but have adverse health outcomes. Recent research has focused largely on acquired mutations in the blood system and shown that acquired mutations are associated with cardiovascular disease, stroke, diabetes, lung disease and other adverse health outcomes. A unifying mechanism is that these acquired mutations result in more inflammation and therefore a diverse range of diseases. However, the breadth of diseases that may be associated with these acquired mutations in the blood are unknown. In large datasets containing genetic information and health outcome information like the UK Biobank it is possible to 1) determine which individuals have acquired mutations in the blood and then 2) test whether carrying these associations is associated with any phenotype (e.g. cardiovascular disease, stroke, arthritis) across all of the phenotypes contained in the UK Biobank. This approach allows the discovery of novel associations and has the potential to drive key new avenues of research. The aim of this study is to conduct a Phenome-wide association study (PheWAS) for the association of acquired mutations in the blood using genotype data with diverse phenotypes. The rationale is to better understand what health outcomes individuals carrying these mutations are at risk for and to guide future research. We anticipate this project taking 24 months and that it has the potential to guide the prevention of adverse health outcomes in people carrying these acquired mutations.
