Principal Investigator: Dr Paul Lacaze
Monash University, Melbourne, AustraliaTags: 47061, ageing, healthy ageing, loss-of-function, penetrance, polygenic risk, risk depletion
Our research aims to determine if genetic risk factors seen in the UK Biobank are the same as those seen in a healthy elderly population from Australia (the ASPREE cohort). In particular, we’d like to test whether there are differences in the frequency or severity of known genetic risk factors between the two populations. We would also like to test for protective genetic factors in the healthy elderly, which might off-set disease risk.
Aim 1: To compare the distribution and frequency of common genetic risk factors (inferring risk of common disease) between the UK Biobank and the ASPREE cohort.
Aim 2: To compare the frequency, distribution and medical relevance of rare, damaging genetic risk factors between the populations, and determine if they are depleted in the healthy elderly across a range of disease outcomes.
Aim 3: To compare the frequency, distribution and medical relevance of protective genetic factors in the healthy elderly.
This project is expected to last for many years, as we plan to continue to monitor the health of the ASPREE healthy elderly population for another 5 years, or more.
The public health impact of our research includes improving the understanding of human genetic variation, helping understand how genetic factors contribute to disease risk, and helping understand how genetic factors may contribute to positive health outcomes, such as healthy ageing. This is particularly relevant given the growing burden of ageing populations in many countries around the world, and the uncertainty with regards to the contribution of genetic versus environmental factors.
Extending the scope
A recent release of UKBB 50,000 exomes data on a global scale is fantastic. We would like to extend the scope of our current project and request to access the UKBB 50,000 exome sequencing data.
- Deep analysis of predicted loss of function protein-disrupting variants between UKBB (sequencing data) and ASPREE (sequencing data) to compare frequency, distribution and medical relevance.
B. To discovery novel rare protective loss of function variants by analyzing UKBB and ASPREE cohorts for multiple phenotypes such as cancer, dementia and CVD.
Last updated Jun 10, 2019