Predicting the risk of heart disease, diabetes and more using millions of gene variants

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Up to 25 million Americans could face triple the normal risk of coronary artery disease, new research suggests. (Connor Wells/Unsplash)

If physicians could predict which of their patients are more likely to develop serious diseases like breast cancer, type 2 diabetes and coronary artery disease, they could offer personalized preventive care that’s only minimally available today. Scientists at the Broad Institute of MIT and Harvard say they’ve developed a genomic screening tool that can predict the risk not only of those three diseases, but also of atrial fibrillation and inflammatory bowel disease.

"We've known for long time that there are people out there at high risk for disease based just on their overall genetic variation," Sekar Kathiresan, director of the cardiovascular disease initiative at the Broad Institute, said in a statement. "From a public health perspective, we need to identify these higher-risk segments of the population so we can provide appropriate care."

The Broad team worked with researchers at Massachusetts General Hospital (MGH), and Harvard Medical School to develop a method for scoring disease risk based on data previously generated about the five conditions and gene mutations that contribute to them. For each disease, they used an algorithm to combine all the contributing gene variants into a single risk score, according to the statement. Then they took genomic data from more than 400,000 people that are stored in the U.K. Biobank and used the algorithms to predict each person’s risk of developing those diseases.

The technique, called “polygenic risk scoring,” uncovered 8% of participants in the U.K. Biobank who were more than three times as likely to develop coronary artery disease as everyone else in the registry, according to the statement. It also found that 1.5% of people in the biobank had triple the risk of breast cancer. The research was published in Nature Genetics.

Co-author Amit Khera, an MGH cardiologist, noted that many of the people found to be facing an elevated risk of heart disease didn’t have any other warning signs, such as high cholesterol. "If they came into my clinical practice, I wouldn't be able to pick them out as high risk with our standard metrics,” he said.

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There are millions of gene variants that have been tied to serious illnesses, prompting efforts to match genetic abnormalities with disease risk—and to develop easy-to-use tools clinicians might someday employ in everyday practice. In June, a team led by the London-based Institute of Cancer Research, for example, announced it had identified 63 new gene mutations that raise the risk of prostate cancer, which the team believes can be combined with 100 previously identified variants to identify men who are six times more likely than the general population to develop the disease.

MGH’s Khera believes the ability to pinpoint patients facing the highest risk of developing serious diseases will help physicians target screening programs for early detection and treatments more effectively. But first, the polygenic risk scores for the five conditions in the Broad-led study would need to be optimized to include more ethnic groups, because the polygenic risk scores were developed based largely on people of European ancestry, the researchers say.

Still, the data generated from the U.K. biobank suggest that millions more people around the world face a high chance of developing serious diseases—and they may not be aware of that risk. For example, they say, their data suggest that up to 25 million Americans face triple the normal risk of coronary artery disease.

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