How Genetics Data Can Lead to the Early Detection of Cardiovascular Disease

Genome sequencing research on 50,000 people may lead to finding heart disease before it strikes.

Coronary artery disease (CAD) is the most common form of heart disease in the United States and claims more than 370,000 lives each year. Although preventive therapies can lessen risk, for some people the first sign of CAD is a heart attack. That’s why early detection is a public health priority — and the goal of important new genetic research at Washington University School of Medicine in St. Louis.

“One of the unique aspects of coronary disease is that there’s a long asymptomatic phase,” says Nathan Stitziel, MD, PhD, director of the Center for Cardiovascular Genetics and assistant director of the McDonnell Genome Institute at the School of Medicine. “If you can find people before they have a clinical event, you can potentially target preventive therapies to those individuals.”

Through large-scale genetic research on CAD, Dr. Stitziel is hoping to gain a better understanding of how to identify people who are at high risk and how to develop new therapies to treat them. “With CAD, there is actually something we can do to prevent the disease,” he says. “Whereas with some other genetic conditions, you may identify people that are at high risk, but you can’t do anything to modify the risk.”

Unprecedented Data Analysis

Dr. Stitziel is helping to lead a federally funded genome sequencing study that will analyze DNA samples from a small study at Washington University School of Medicine, as well as those collected over several decades in prior studies around the world. The unprecedented analysis of 25,000 people with CAD and 25,000 people without the disease will be done at the McDonnell Genome Institute and two other sequencing centers, and is scheduled to take several years.

“We’re going to sequence their entire genomes,” Dr. Stitziel says. “We will have billions of data points for those 50,000 individuals to try to make sense of what exactly is going on.”

The science of informatics and its ability to find patterns in large data sets will be essential in managing the massive amount of information in the study. “There are literally hundreds of terabytes and even petabytes of data,” Dr. Stitziel says. “That is certainly one of the strengths of informatics. It allows you to deal with big data in a meaningful way.”

The innovative research is also made possible due to recent advances in sequencing technology, Dr. Stitziel says. “The cost and the time to do sequencing has plummeted faster than any other technology that I know of,” he says. The initial Human Genome Project, completed in 2003, cost $1 billion and took 13 years. Today, the cost to sequence a genome is about $1,500, and the process takes only a matter of days.

Expanding Genetic Testing to the Entire Genome

An underlying goal of the research, as well as other studies that Dr. Stitziel is conducting, is to expand the scope of genetic testing in the clinical setting. Currently, the field of genetics addresses disorders that are under the regulation of single genes. These conditions are known as Mendelian disorders, named after Gregor Mendel, whose plant experiments in the mid-1800s were the basis for many of the rules of heredity. They include cystic fibrosis, sickle cell anemia and Huntington disease, as well as cardiovascular conditions such as high cholesterol.

What is not as well understood is how people may have a predisposition to disease because of two or more genes, known as polygenic inheritance or complex genetic inheritance. “We have an active research path that is trying to understand how we can use genetic information from across the whole genome to predict somebody’s risk for coronary disease,” Dr. Stitziel says. “It’s an informatics problem: How do you incorporate information from across the entire genome to try and predict somebody’s risk of having disease?”

So far, his research team has analyzed portions of the genome and identified 20 percent of the population that has a significantly increased risk for heart attack. “It’s not clinically approved, so you can’t walk into a clinic and order that [test],” he says, “but potentially someday it will actually make it into clinical practice.”

For Dr. Stitziel, who is a cardiologist and also holds a doctorate degree in bioinformatics, studying heart disease in the context of genetics and big data is a natural fit and has great potential to improve the lives of patients. “We finally have the ability to generate large-scale genetic data in humans, really for the first time,” he says. “This kind of idea would be completely impossible 10 years ago.”

“It’s an informatics problem: How do you incorporate information from across the entire genome to try and predict somebody’s risk of having disease?”