Genetic protection against disease in the healthy elderly

Genetic variants (DNA changes) can result in increased risk of diseases like cancer, cardiovascular disease and dementia. However, some DNA changes can be protective, and reduce risk of such diseases. Protective genetic variants play an important role in reducing disease risk, and have informed the development of drug therapies, including for cardiovascular disease (CVD). If we can better understand the role protective genetic factors play in reducing risk, it may lead to more therapeutic and preventive targets. The healthy elderly who survive to advanced age without disease are more likely to carry protective genetic variants. Yet the healthy elderly, to date, have not been made the focus of large human genetic studies for protective variants. This PhD and research program will focus on the genetic analysis of one of Australia’s largest healthy elderly cohorts, the ASPREE cohort. ASPREE has collected blood samples from 15,000 healthy elderly Australians aged >70 years with no CVD history, and measured a range of outcomes over 5+ years. I drive the genetic program for ASPREE, and my research assesses the relative contributions of genetic risk factors, and protective factors, in modifying risk of disease in this population. ASPREE is enriched for healthy elderly individuals with exceptional cardiovascular health. However, there are sub-sets of ASPREE participants at high genetic risk, who defy the odds, and remain unaffected despite high genetic risk. This includes carriers of gene changes that increase risk of cancer, high cholesterol, structural heart problems and sudden cardiac death. Because these individuals are at high genetic risk of disease, yet remain unaffected by disease, they have an increased likelihood of carrying protective genetic factors. Analysing the genomes of these resilient cases will provide a unique opportunity to discover protective genetic variants. As a supervisor, I have valuable scientific experience from both academia and industry, and have established one of the first Public Health Genomics programs in Australia, centred around large-scale population DNA sequencing analysis and clinical data from prevention trials. This PhD will be computational in the School of Public Health, with skills developed in statistical and population genetics, epidemiology, computational biology, bioinformatics and DNA sequence analysis.