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Polygenic Risk Scores Predict Heart Disease in French-Canadian Cohort

NEW YORK (GenomeWeb) – Two polygenic risk scores for coronary artery disease that were developed using UK Biobank data can also predict heart disease in a French-Canadian cohort, a new study has found.

The genome-wide polygenic risk scores were developed recently to predict people's risk of developing coronary artery disease, which accounts for nearly a third of deaths worldwide, based on millions of genetic variants. While these risk scores appeared to be accurate in initial studies, researchers from the Montreal Heart Institute and the University of Montreal sought to determine whether they could also be applied to French-Canadian individuals.

As they reported today in Circulation: Genomic and Precision Medicine, the researchers found that while the polygenic risk scores could pick out French-Canadian individuals at high risk of having a future heart attack, the scores were not good at predicting new cardiac events among individuals who had already experienced one.

 "The PRS is like having a snapshot of the whole genetic variation found in one's DNA and can more powerfully predict one's disease risk," lead author Guillaume Lettre from the Montreal Heart Institute and the University of Montreal said in a statement. "Using the score, we can better understand whether someone is at higher or lower risk to develop a heart problem."

Last August, researchers led by Massachusetts General Hospital's Sekar Kathiresan reported in Nature Genetics that they had generated a polygenic risk score based on some 6.6 million common SNPs to identify individuals at increased risk of developing cardiovascular disease. Similarly, last October, the University of Leicester's Nilesh Samani in the UK and his colleagues reported in the Journal of the American College of Cardiology that they also developed a genomic risk score for coronary artery disease, based on 1.7 million SNPs. Both groups relied on UK Biobank data. 

In their new study, Lettre and his colleagues applied these two scores to 3,309 individuals from the Montreal Heart Institute Biobank and 5,762 individuals from the CARTaGENE research platform. Among these French-Canadian cohorts, the researchers were able to validate both polygenic risk scores and noted the scores were highly correlated with each other. In particular, the researchers found that a increase of one standard deviation in either polygenic risk score was associated with a more than 60 percent increase in cardiovascular disease risk.

This suggested to the researchers that the scores, which were developed in individuals of European ancestry, performed well even among the more genetically and environmentally homogenous French-Canadian population.

Some familial hypercholesterolemia cases in French-Canadians in Quebec are due to a 15-kilobase deletion in the LDLR gene, Lettre and his colleague noted. Within the 1,964 Montreal Heart Institute biobank participants with available whole-genome sequencing data, the researchers identified 14 heterozygous carriers of that mutation, 12 of whom had coronary artery disease.

The researchers estimated that polygenic risk scores could identify between 6 percent and 7 percent of the French-Canadian population that are at high risk of coronary artery disease, having the same or higher risk than LDLR mutation carriers.

"Using the polygenic risk score, even in a normal population, we can find people whose risk is as high as those who have this rare disease," Lettre said.

The polygenic risk scores did not fare as well, though, in predicting new cardiac events in individuals who had already had a heart attack, the researchers added. They speculated that this could be due to those patients' increased age as well as the fact that about three-quarters of these individuals were on statin treatments.

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