ArticleCirculation2022
Predictive Utility of a Validated Polygenic Risk Score for Long-Term Risk of Coronary Heart Disease in Young and Middle-Aged Adults.
Article in Circulation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- A dual domain systematic review and meta-analysis of risk tool accuracy to predict cardiovascular morbidity in prehypertension and diabetic morbidity in prediabetes.Frontiers in endocrinology · 2025Pooled it
- Cost-Effectiveness of Polygenic Risk Score-Guided Statin Therapy for Cardiovascular Disease Prevention in Singapore.JACC. Asia · 2026Article
- Associations of cholesterol, high-density lipoprotein and glucose index and triglyceride-glucose-related indices with carotid atherosclerosis in young and middle-aged individuals.Frontiers in endocrinology · 2026Article
- Mechanisms of Inflammation Chronification: Gene and Epigenetic Regulation of Intolerant Response (Trained Immunity).Current medicinal chemistry · 2026Article
- Advanced machine learning techniques for coronary artery disease risk prediction in early middle-aged adults.BMC medical genomics · 2025Article
- Differential Performance of Polygenic Score for Coronary Artery Disease Based on Coronary Artery Calcium Between Men Living With and Without HIV.Journal of the American Heart Association · 2025Article
- Hypothesis test of specific parametric structure in a generalized additive model.medRxiv : the preprint server for health sciences · 2025Article
- Review
- Recent Advances in Stroke Genetics-Unraveling the Complexity of Cerebral Infarction: A Brief Review.Genes · 2025Review
- Polygenic Prediction of Recurrent Events After Early-Onset Myocardial Infarction.Circulation. Genomic and precision medicine · 2024Article
- Considering Social and Genetic Factors in Cardiovascular Disease Risk.Journal of the American College of Cardiology · 2024Article
- Joint impact of polygenic risk score and lifestyles on early- and late-onset cardiovascular diseases.Nature human behaviour · 2024Article
- Development of machine learning-based models to predict 10-year risk of cardiovascular disease: a prospective cohort study.Stroke and vascular neurology · 2023Article
- Polygenic Risk, Rare Variants, and Family History: Independent and Additive Effects on Coronary Heart Disease.JACC. Advances · 2023Article
- Polygenic risk score in comparison with C-reactive protein for predicting incident coronary heart disease.Atherosclerosis · 2023Article
- Molecular Biomarkers for Cardiometabolic Disease: Risk Assessment in Young Individuals.Circulation research · 2023Review
- The necessity of incorporating non-genetic risk factors into polygenic risk score models.Scientific reports · 2023Article
- Advances and Applications of Polygenic Scores for Coronary Artery Disease.Annual review of medicine · 2023Review
- Genetic Variants Associated with Hypertension Risk: Progress and Implications.Pulse (Basel, Switzerland)Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundUnderstanding the predictive utility of previously derived polygenic risk scores (PRSs) for long-term risk of coronary heart disease (CHD) and its additive value beyond traditional risk factors can inform prevention strategies.
methodsData from adults 20 to 59 years of age who were free of CHD from the FOS (Framingham Offspring Study) and the ARIC (Atherosclerosis Risk in Communities) study were analyzed. Because the PRS was derived from samples of predominantly European ancestry, individuals who self-reported White race were included. The sample was stratified by age and cohort: young (FOS, 20-39 years [median, 30 years] of age), early midlife (FOS, 40-59 years [median, 43] years of age), and late midlife (ARIC, 45-59 years [median, 52 years] of age). Two previously derived and validated prediction tools were applied: (1) a 30-year traditional risk factor score and (2) a genome-wide PRS comprising >6 million genetic variants. Hazard ratios for the association between each risk estimate and incident CHD were calculated. Predicted and observed rates of CHD were compared to assess discrimination for each model individually and together with the optimism-corrected C index (95% CI).
resultsAmong 9757 participants, both the traditional risk factor score (hazard ratio per 1 SD, 2.60 [95% CI, 2.08-3.27], 2.09 [95% CI, 1.83-2.40], and 2.11 [95% CI, 1.96-2.28]) and the PRS (hazard ratio, 1.98 [95% CI, 1.70-2.30], 1.64 [95% CI, 1.47-1.84], and 1.22 [95% CI, 1.15-1.30]) were significantly associated with incident CHD in young, early midlife, and late midlife, respectively. Discrimination was similar or better for the traditional risk factor score (C index, 0.74 [95% CI, 0.70-0.78], 0.70 [95% CI, 0.67-0.72], and 0.72 [95% CI, 0.70-0.73]) compared with an age- and sex-adjusted PRS (0.73 [95% CI, 0.69-0.78], 0.66 [95% CI, 0.62-0.69], and 0.66 [95% CI, 0.64-0.67]) in young, early-midlife, and late-midlife participants, respectively. The ΔC index when PRS was added to the traditional risk factor score was 0.03 (95% CI, 0.001-0.05), 0.02 (95% CI, -0.002 to 0.037), and 0.002 (95% CI, -0.002 to 0.006) in young, early-midlife, and late-midlife participants, respectively.
conclusionsDespite a statistically significant association between PRS and 30-year risk of CHD, the C statistic improved only marginally with the addition of PRS to the traditional risk factor model among young adults and did not improve among midlife adults. PRS, an immutable factor that cannot be directly intervened on, has minimal clinical utility for long-term CHD prediction when added to a traditional risk factor model.
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