Research shows polygenic risk scores (PRS) modestly but significantly improve risk predictions for atherosclerotic cardiovascular disease in the diverse Million Veteran Program cohort.
Writing in JAMA Cardiology, Jason Vassy, an associate professor at Harvard Medical School and a clinician at Veterans Affairs Boston Healthcare System, and colleagues report that having a high PRS was associated with increased cardiovascular risk in all groups, but the association was greater in women and younger age groups and also in non-Hispanic White individuals.
“Atherosclerotic cardiovascular disease is a tremendous source of morbidity and mortality globally,” write the authors.
“Primary prevention with statin and aspirin therapy can significantly decrease this burden; however, estimating patient risk is a key first step to identifying patients who would benefit.”
PRS, which involve adding up the risk contributed by a range of different mutations, such as single-nucleotide polymorphisms, are increasingly being used to improve disease risk prediction.
“Advances in statistical methods, computational capability, and the size of genome-wide association studies (GWAS) for discovery have improved the performance of PRS in discriminating disease cases from controls and estimating risk of incident disease,” note Vasy and team.
However, a problem with many PRS is that they are often based on the results of GWAS that were primarily carried out on individuals of non-Hispanic White European origin. This can make it more difficult to assess disease risk in people of different ethnic origins, as the prevalence of disease contributing mutations does vary across different populations around the world.
The Million Veteran Program is a large and diverse biobank with genetic, survey, and electronic health record data collected on its participants. In this study, Vassy and colleagues assessed the benefits of using pre-existing cardiovascular risk PRS to estimate risk of nonfatal myocardial infarction (MI), ischemic stroke, atherosclerotic cardiovascular disease death, and composite cardiovascular events.
Overall, 79,151 participants (mean age 58 years; 87% male) were included in the study. Of these, 18, 505 were non-Hispanic Black (23.4%), 6785 Hispanic (8.6%), and 53,861 non-Hispanic White (68.0%).
Have a high PRS increased the risk for MI over several years of follow-up by 10%, 26%, and 23%, in non-Hispanic Black, Hispanic, and non-Hispanic White individuals, respectively, compared with a low PRS. Similarly, stroke risk was increased by 15% in non-Hispanic White individuals with a high PRS.
The combined PRS score was also linked to combined cardiovascular events, with a 20%, 11%, and 12% increase in risk for non-Hispanic White, non-Hispanic Black, and Hispanic participants, respectively. Having a high PRS score had a more substantial impact on risk in women than men and in younger vs older individuals.
“Results of this prognostic study suggest that PRS for coronary artery disease and ischemic stroke derived from largely European ancestry populations were statistically significantly associated with first atherosclerotic cardiovascular disease events in the multi-ancestry Million Veteran Program cohort,” write the authors.
“This study also reinforces the need for multi-ancestry PRS to improve risk stratification of non-European populations.”
