Polygenic scores did not show a meaningful benefit for risk stratification in heart disease in two studies published in the February 18 issue of the Journal of the American Medical Association.
One study evaluated risk scoring in a cohort of participants in UK Biobank, a nonprofit research project that is performing whole genome sequencing on a mass scale in the U.K. The observational study assessed polygenic risk scores, pooled cohort equations (risk prediction models), and both combined for predicting events in 352,660 participants with no cardiovascular disease at baseline.
"The addition of a polygenic risk score for [coronary artery disease (CAD)] to pooled cohort equations was associated with a statistically significant, yet modest, improvement in the predictive accuracy for incident CAD and improved risk stratification for only a small proportion of individuals," Ioanna Tzoulaki, PhD, a lecturer at Imperial College London, and colleagues wrote (JAMA, February 18, 2020, Vol. 323:7, pp. 636-645).
The second study reported in JAMA evaluated polygenic risk scoring in population-wide screening for coronary heart disease. Dr. Jonathan Mosley, PhD, an assistant professor of medicine at Vanderbilt University, and colleagues examined the value of scoring on a retrospective basis, using data for participants with European ancestry in the Atherosclerosis Risk in Communities (ARIC) study and the Multi-Ethnic Study of Atherosclerosis (MESA).
"In this analysis of [two] cohorts of [U.S.] adults, the polygenic risk score was associated with incident coronary heart disease events but did not significantly improve discrimination, calibration, or risk reclassification compared with conventional predictors," Mosley et al wrote (pp. 627-635).
Editorial: Clinical value currently lacking
The likelihood of developing heart disease and cardiovascular events in asymptomatic people is typically measured through the modeling of 10-year risk. There has been a lot of progress in the past decade in identifying genetic variants/single-nucleotide polymorphisms associated with coronary artery disease, but more clarity is needed on the value of polygenic risk scoring beyond available risk modeling, Tzoulaki and colleagues noted.
Both analyses -- by Tzoulaki et al and Mosley et al -- were rigorously conducted and add to prior research that did not find a meaningful benefit for adding polygenic risk scores to pooled cohort equations, according to an editorial also published in the February 18 issue (pp. 614-615). The results show that, currently, polygenic risk scores do not offer clinical utility for preventing CAD in middle-aged adults of European descent, wrote Dr. Sadiya Khan, an assistant professor of medicine at Northwestern University, and colleagues.
"In the meanwhile, the best approach for prevention of CAD continues to be a combination of population-wide risk factor approaches for the entire population and addition of drug therapies and lifestyle interventions according to guidelines developed by the American Heart Association and American College of Cardiology," Khan and colleagues concluded.