Is PRS testing the future of chronic disease prevention?
Genome wide association studies (GWASs) from more inclusive datasets are needed to improve the relevance of PRS across ancestry groups, the authors write.
Dr. Vassy points out that “the risk estimates from GWAS are the underpinnings of the polygenic scores, so a score is only as valid as its original.” Fortunately, he adds, “advances are occurring on multiple fronts, and this will be key to promoting the equitable implementation of polygenic scores. Larger, more diverse cohorts are being recruited for GWAS studies, and more sophisticated, trans-ancestry statistical GWAS methods are being developed to analyze these more diverse data.”
In England, researchers are considering the benefits of using polygenic scores in National Health Service checks for cardiovascular disease, a well-studied area of genetic risk. The new article and the English effort draw from the PGS Catalogue, an open database built by Samuel Lambert, of the University of Cambridge Department of Public Health and Primary Care, and his colleagues to provide scores and methods that can be reused and adapted for clinical use.
He says he’d recommend PRS with confidence to his family members – in particular, certain in-depth cancer assays – “provided [the results] would be interpreted in collaboration with a health care professional who understands genetics (for example, a genetic counselor) with carefully vetted information on the validity and actionability of the test result.”
Mr. Lambert feels it’s important to understand that PRS testing isn’t deterministic. “The risk information is inherently probabilistic and relative (for example, you have a four times higher risk than the average person, but if the disease prevalence is 0.5%, this is a small absolute difference),” he says.
“The PRS also explains a fraction of the variability of risk in the population and thus shouldn’t be used alone but in combination with other established risk factors and tools to predict future risk when they exist,” Mr. Lambert says.
“And thirdly, most current PRS are less accurate in those of non-European ancestry due to a lack of ancestral diversity in the cohorts and datasets that have been used to develop these PRS; special attention must be paid to make sure that the PRS results are valid for the individual,” he adds.
Funding for the study was provided by the NIH National Human Genome Research Institute and NIH, the American Heart Association, the National Heart, Lung and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, and Massachusetts General Hospital. Dr. Vassy is an employee of the U.S. Department of Veterans Affairs; the views expressed do not represent those of the VA or the U.S. government. Mr. Lambert is an employee of Cambridge-Baker Systems Genomics Initiative, Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care.
A version of this article first appeared on Medscape.com.