Approved research

Comprehensive study of mosaic loss of chromosome Y in aging males and predisposition to cancer as well as Alzheimer's disease using the UK Biobank cohort.

Lay summary

We have recently made three discoveries related to acquired Loss Of chromosome Y (LOY) in blood cells of aging men. LOY is associated with: a) shorter survival and increased mortality from cancers; b) Alzheimer?s disease (AD); and c) smoking of tobacco, suggesting that smoking induces LOY. These findings are a basis for research towards understanding why LOY causes cancer and AD in males. Our aim is to further explore LOY as a disease biomarker in ~250,000 males of UK Biobank and (using the female cohort) investigate chromosome X to search for corresponding mechanisms that operate in women. The questions, which are the focus of our application, are clearly of public health importance. The results may significantly improve our understanding of the risks for cancer, Alzheimer?s disease and perhaps other morbidities in men, and possibly also in women. Cancer and Alzheimer?s disease diagnoses are relevant for >50% of morbidity and/or mortality in aging human population. Our project could also be critical in identifying an extreme at-risk subgroup for beneficial health interventions. We will use Axiom data to measure LOY in males. This information is not available from standard output and requires intensity data from the Axiom genotyping. We will also correlate LOY with smoking, mortality, cancer, Alzheimer?s disease (AD) and other outcomes. In parallel, we will investigate whether chromosome aberrations occurs in the blood of women, by looking for loss (full or partial) of the X chromosome in Axiom data. Full cohort for Axiom data and health information will be required.