Genetic protection against cardiovascular disease

Dr Paul Lacaze, Monash University

2019 Future Leader Fellowship

Years funded: 2020-2023

Protective genetic variants play an important role in reducing cardiovascular disease (CVD) risk, and have informed the development of drug therapies for CVD. If we can better understand the role protective genetic factors play in reducing CVD risk, it may lead to more therapeutic and preventive targets. The healthy elderly who survive to advanced age without CVD 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 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 CVD outcomes over 5+ years. I drive the genetic program for ASPREE, and my research will assess the relative contributions of genetic risk factors, and protective factors, in modifying risk of CVD 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 of CVD, who defy the odds, and remain unaffected by CVD despite high genetic risk.

This includes carriers of gene changes that increase risk of high cholesterol, structural heart problems and sudden cardiac death. Because these individuals are at high genetic risk of CVD, 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 for CVD. 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 cardiovascular prevention trials. This provides an exceptional platform for future success.