Genetic map of the heart opens new ways of understanding heart disease
Published: 03 Sep 2020
Heart disease is the top cause of death worldwide and in Singapore, it accounts for one third of all deaths each year. It is a complex set of diseases that is influenced by many different genes.
To better understand the genetic basis of such complex diseases and identify the important interactions involved in heart disease, Professor Roger Foo of the Department of Medicine, NUS Yong Loo Lin School of Medicine and Senior Consultant at the National University Heart Centre, National University Hospital (NUH), has led a team of researchers to develop the first heart genomic “connectome”.
This connectome is a map of the genes in the heart and the “switches” that connect to and control them. This would allow researchers to study how the different parts of the genome (made up of both genes and the non-coding elements between them) interact physically with one another inside the tight, small space of the nucleus.
“Humans have the same number of genes as flies or worms—around 20,000,” explained Prof Foo. “What makes us more complex than a fly is that we have a lot more switches that turn these genes on or off.”
The switches are mostly in the non-coding elements in the genome, i.e. the portions of DNA between genes. They can be flipped on or off according to differences in the DNA code at the section of the switch, which are called variants. For example, in one individual, a variant G may mean that the switch is flipped on. In another individual, a different variant A may mean that the switch stays off.
To make things more complicated, each gene has more than one switch, and switches may be very far away from the genes they control, making it difficult to identify which switch controls which gene just from looking at the DNA code.
The connectome map developed by the NUS Medicine team shows where these switches are and also pinpoints the most important switches for each gene in the map. Significantly, they found that a series of 59 new variants influencing key switches for particular genes may play an important role in the function of those genes in heart disease.
“Our connectome helps to make sense of the human genome by highlighting the sections and interactions that are relevant for various organs, such as the heart. This could make it possible to analyse the functions of the entire genome someday.” – Professor Roger Foo
This work was published as two companion publications in the journals Circulation and Circulation Research. The papers were co–first-authored by Assistant Professor Chukwuemeka George Anene-Nzelu, PhD students Wilson Tan and Mick Lee, as well as Dr Eleanor Wong.
Added Asst Prof Anene-Nzelu, “Using the connectome, we were also able to identify new genes associated with heart disease. These could serve as targets for the development of novel treatments for these diseases.”
The researchers are part of the Cardiovascular Disease Translational Research Programme, one of nine new strategic research focus areas established at NUS Medicine in July.
The new focus areas, which also include infectious diseases, healthy longevity and precision medicine, aim to create greater synergy and collaboration between basic and clinical scientists within the National University Health System, and to deliver research outcomes that address current clinical and national healthcare issues.
Professor Chng Wee Joo, Vice-Dean of Research at NUS Medicine, said: “We hope that these nine programmes will deliver not just outstanding research, but over the next five to 10 years, make some real impact on how we treat our patients and on the population’s health.”
