Research

Busselton Family Heart Study

What is CVD?

Cardiovascular disease (CVD) describes diseases of the heart and blood vessels, including heart attack and stroke.
CVD is the leading cause of death in Australia, with 43,946 deaths recorded in 2012 (almost 30% of all deaths in Australia) (1). In terms of economic burden, CVD is the most expensive disease group costing $7.9 billion or 11% of direct healthcare expenditure a year (2).

The causes of developing CVD are complex, with large environmental and genetic contributions to risk. As well as diet and lifestyle factors, susceptibility to CVD is known to have a significant genetic component, however this is not yet well understood.

In the last decade there has been a large push to address this deficit in knowledge about the genetic risk of CVD, with the hope that those individuals most at risk can be identified early and targeted for lifestyle and other interventions.

Our objective

To better understand the heritability of complex diseases, such as CVD, and to identify rare genetic variant risk factors, it is helpful to study data from large, densely affected families in combination with massively parallel sequencing. However, suitable family studies are rare.

In 2016, GOHaD researchers and other colleagues were awarded more than $2 million in funding from the NHMRC (3) to transform the iconic Busselton Health Study (BHS) into a unique Australian family dataset – the Busselton Family Heart Study – that can be used to investigate genetic risk factors for CVD and other complex diseases.

With this project, we are aiming to identify the specific heritable genetic differences between individuals that put us at greater risk of cardiovascular disease. It is anticipated that the identification of causal genetic risk variants will enable early identification of at-risk individuals, and facilitate the development of new drugs to treat and prevent CVD.

We are studying large empirically defined families from the BHS to quantitatively examine the plasma lipidome and identify rare risk variants for CVD that act through effects on the lipidome. In particular, we hypothesise that genetic analysis of the plasma lipidome in large families enriched for CVD events, with a focus on identifying rare mutations, will identify novel CVD risk factors of large effect. These risk factors will have clinical utility in the diagnosis and prediction of CVD.

The specific aims of this research are to:

  • Obtain whole genome sequence (WGS) for BHS individuals in extended family lineages
  • Measure the plasma lipidome in BHS family lineages
  • Identify genomic regions for CVD risk in BHS family lineages using lipid endophenotypes (quantitative traits that are heritable and genetically correlated with disease risk)
  • Identify risk variants/genes in genomic regions influencing CVD risk
  • Evaluate the clinical utility of novel rare CVD risk variants in coronary artery disease and familial hypercholesterolemia

Our overall objective is translation of this knowledge to improve human health. As a first step, we will evaluate the clinical utility of novel risk variants in coronary artery disease and familial hypercholesterolaemia, the most common cause of high cholesterol.

The potential benefit to human health from genetic discoveries arising from this work will make significant contributions to the field internationally.

References
(1) Australian Bureau of Statistics (2012), Causes of Death, Australia, 2012
(2) Australian Institute of Health and Welfare (2012), Australia’s Health 2012
(3) Research Data Australia (2016), The Busselton Family Heart Study [2016-2020]

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