Australian scientists reveal heart disease can be triggered by complex gene networks

Australian scientists have revealed heart disease can be triggered by complex networks of genes that interact on a scale never known before.

Victor Chang Cardiac Research Institute executive director Jason Kovacic.

Australian scientists have revealed heart disease can be triggered by complex networks of genes that interact on a scale never known before, opening the possibility of being able to far more accurately predict a person’s risk of heart disease and allow for better treatments.

The findings from an international team of scientists – including the Victor Chang Cardiac Research Institute in Sydney – present a new avenue for screening life-threatening conditions such as coronary heart disease, Australia’s biggest killer.

The study identified that up to 60 per cent of the risk associated with coronary heart disease may be explained by changes in the activity of hundreds of genes working together in networks across several organs in the body.

The study has been published in the journal Nature Cardiovascular Research. The work was led by senior author Johan L.M. Bjorkegren, from Icahn School of Medicine in New York, who began the study 20 years ago when working as a heart surgeon.

Co-author Jason Kovacic, executive director at the Victor Chang Cardiac Research Institute, says scientists now have a clear picture of how these networks of genes work together to cause heart disease.

“This paper is a huge milestone,” Professor Kovacic said.

“It really is just taking things a quantum leap forward. This may well prove to be a total paradigm-shifting study that will forever reset the way we consider heart ­attack and stroke.

“This opens up the possibility of being able to far more accurately predict a person’s risk of heart disease, which would allow for earlier assessments and potentially better treatments.”

The study examined tissue samples taken from the arterial walls of the heart, as well as blood, liver, skeletal muscle, visceral abdominal and subcutaneous fat. The samples were taken from hundreds of patients who have had open heart surgery, and complex computational methods were used to study gene expression.

“For the first time we now have a comprehensive map of how these genes are operating together,” Professor Kovacic said. “This has never been accounted for until now and shines a whole new light on how and why we are predisposed to heart disease.”

Previous studies have found that about 20 per cent of the risk associated with coronary artery disease may be linked to differences in a person’s DNA sequences, but this new study finds that an ­additional 60 per cent of the risk could be explained by the newly discovered gene networks working together. “This study actually goes an enormous distance to explaining the heritability of coronary artery disease,” Professor Kovacic said.

He said the gene networks interact with lifestyle risk factors such as high cholesterol and high blood pressure. Treatments may be able to be developed that reverse atherosclerosis in the arteries in high-risk patients.

“By targeting those gene networks, we suspect there’s a very high likelihood we’d be able to ­favourably modify plaques,” Professor Kovacic said. “This research will be central to the development of ‘precision medicine’ – where ­patients are diagnosed and treated depending on how their unique genetics interact with risk factors in the environment.”

And he said the discovery may also be important for diagnosing risk and treating a number of other conditions.

“It may also eventually see us altering problem genes at the top of the gene network, which can impact the hundreds or thousands of genes below and lessen the risk from certain conditions.

“In addition, it’s almost certain that these gene networks are critical to many other human diseases like high blood pressure, diabetes, and stroke.”