Scientists have a new test to calculate a person’s risk of early-onset heart disease, taking into account multiple genetic differences to generate a “polygenic risk score.” From the American Heart Association, lead author Sébastien Thériault MD, MSc, FRCPc, says the new test should be added to the “genetic investigation of patients with very early coronary artery disease.”
Coronary artery disease, the most common form of heart disease, is most often caused by a slew of lifestyle factors that individuals can typically avoid, such as smoking, physical inactivity, poor diet, and high levels of cholesterol, blood pressure, and blood sugar. When the cause of heart disease isn’t related to lifestyle choices, avoiding its onset can be less avoidable and more unpredictable.
For example, a dominant genetic defect on chromosome 19 called familial hypercholesterolemia (FH) causes increased levels of “bad” cholesterol, low-density lipoprotein. This defect is the most common cause of inherited high cholesterol, and it affects about one in 500 people. Individuals with the FH defect suffer an elevated risk of early-onset heart disease, defined by developing before 40 for men and before 45 for women. Early diagnosis and treatment are especially important for this high-risk group.
Although FH is an important factor to consider, it is not the only single genetic defect to cause heart disease, and many other defects aren’t detectable with existing diagnostic tests. Using the new approach, researchers believe they can make better predictions than standard tests for single genetic defects.
With 126 total participants with early-onset heart disease - none with the FH defect - and 111,283 control participants without early-onset heart disease, Thériault and the other researchers from the study showed how their new risk score could successfully predict early-onset heart disease.
They were able to show that the new risk score predicted risk of early-onset heart disease just as well as tests for FH - detecting a high risk in 1 out of 53 individuals. The risk score is generated via scanning for 182 genetic differences connected to coronary artery disease.
"The increase in genetic risk was independent of other known risk factors, suggesting that testing for multiple genetic differences is clinically useful to evaluate risk and guide management," said senior author Guillaume Paré, MD, MSc, FRCPc. "Combining polygenic screening with current testing for familial hypercholesterolemia could potentially increase five-fold the number of cases for which a genetic explanation can be found."
The present study was published in the journal Circulation: Cardiovascular Genetics.