Single polygenic risk score predicts early-onset heart disease with most accuracy to date

A cardiovascular risk score based on polygenic testing has proven more effective for detecting early-onset heart disease than run-of-the-mill genetic screenings, researchers reported this month in Circulation: Genomic and Precision Medicine.

As heart disease continues to plague the United States and communities abroad, clinician-recommended measures like quitting smoking, tracking blood pressure, increasing exercise and maintaining a healthy diet remain tried-and-true techniques for lowering cardiovascular risk. High blood levels of low-density lipoprotein (LDL) cholesterol, when left untouched, can lead to complications like coronary artery disease.

However, a fraction of high-LDL cases are a result of a genetic defect known as familial hypercholesterolemia (FH), senior author Guillaume Paré, MD, MSc, and colleagues wrote in their study—and those instances can be hard to detect. One modern test can identify the defect, the authors wrote, but FH is unique in that way. For most candidates of early-onset heart disease, red flags are few and far between.

Paré et al. created a single polygenic risk score based on not only FH indicators but 182 genetic differences related to coronary artery disease, according to the study. Hundreds of thousands of European patients were tested across the United Kingdom, most of whom weren’t affected by early-onset heart disease.

The research team found the polygenic risk score predicted a high risk for early-onset heart disease in one of 53 patients at the same level as someone with FH. The single genetic test for FH predicts a prevalence of 1 in 256 individuals.

“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,” Paré said in a release from the American Heart Association. “Combining polygenic screening with current testing for familial hypercholesterolemia could potentially increase five-fold the number of cases for which a genetic explanation is found."