Cardiovascular disease: The rise of the genetic risk score
Open accessAbstract
points• Use of risk factors for decision-making in cardiovascular disease has a long history in medicine.• Early attempts to augment traditional risk factors with genetic risk scores were hampered by too little understanding of the genetic basis of complex cardiovascular disease.• Newer studies based on hundreds of thousands of people and millions of genetic variants indicate that genetic risk scores can now outperform traditional risk factors in risk prediction.• We propose the time has come to incorporate genetic risk scores into clinical practice.• Studies should focus on the most appropriate way to do this to maximize benefit for our patients."[However,] epidemiologic information has accumulated which now allows the physician to recognize certain characteristics of increased risk in patients he [sic] sees in his practice.Some of these characteristics have been convincingly demonstrated, others are still under investigation.More precise identification will undoubtedly be possible in the future."-WilliamKannel, Director, Framingham Heart Study [1] In a classic paper [1], Kannel reported the early results of the longitudinal Framingham Heart Study, demonstrating the identification of factors (for which he coined the term "risk factors") that "precede the development of overt coronary heart disease in humans".Later, the Framingham Risk Score was formalized to include age, sex, diabetes, smoking status, total cholesterol, high-density lipoprotein (HDL) cholesterol, and blood pressure [2], providing a framework for cardiovascular disease (CVD) risk assessment to which all others are compared.Intuitively, the burden of these risk factors accumulates over time (e.g., pack years of smoking or years of hypertension), and some newer risk models allow input of risk factor data from multiple time points [3].While repeated measurement of CVD biomarkers such as total cholesterol may improve risk prediction, lifelong exposure to CVD risk factors is better captured by genetic susceptibility [4].Thus, the quest to improve risk prediction for CVD has naturally come to focus on the development of genetic risk scores [5].This has only been possible because of robust, replicable
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Cardiovascular research has led the charge towards clinical translation of PRS.
“Cardiovascular research, for example, has led the charge towards clinical translation of PRS1.”
From Clinical use of current polygenic risk scores may exacerbate health disparities (2019) · cites this paper as [1]
The Summary points describe a cardiovascular pilot study that showed the feasibility of delivering a genetic risk score in a clinical setting, and the authors propose incorporating such scores into practice. They also say few studies have addressed practical implementation. The paper does not establish that cardiovascular research has led other fields in clinical translation. (LLM, conf=0.83)
Experimental — accuracy not yet measuredMany earlier criticisms of limited prediction power are now recognized to have been chiefly an issue of insufficient sample size, which is no longer the case for many outcomes.
“Many earlier criticisms of limited prediction power are now recognized to have been chiefly an issue of insufficient sample size, which is no longer the case for many outcomes1.”
From Clinical use of current polygenic risk scores may exacerbate health disparities (2019) · cites this paper as [1]
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Clinical use of current polygenic risk scores may exacerbate health disparities
Martin, A. R., Kanai, M., Kamatani, Y., Okada, Y., Neale, B. M., & Daly, M. J. (2019) · Nature Genetics · doi:10.1038/s41588-019-0379-x · Cited by 2,831 · see citing works
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Current clinical use of polygenic scores will risk exacerbating health disparities
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- Authors
- Knowles, J. W., & Ashley, E. A.
- Affiliations
- Stanford Medicine (US)
- Corresponding author
- Ashley, Euan A.
- Venue
- PLOS Medicine
- Publisher
- Public Library of Science (PLoS)
- Published
- 2018-03-30
- Volume
- 15
- Issue
- 3
- Pages
- e1002546
- ISSN
- 1549-1277 (ISSN-L)
- 1549-1676
- PMC
- PMC5877829
- OpenAlex
- W2794819865
- Cited by
- 182
- References
- 5
- Citations by year
- 2026: 2 · 2025: 14 · 2024: 12 · 2023: 27 · 2022: 31 · 2021: 28 · 2020: 23 · 2019: 32 · 2018: 13
- FWCI
- 14.69
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS Medicine (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (NIH-R01)
- National Heart, Lung, and Blood Institute (R01HL126527, R01HL113006, R01HL130020, T32HL094274)
- National Human Genome Research Institute (U01HG007436, U01HG007708)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK107437)
- National Institute of Biomedical Imaging and Bioengineering (U24EB023674)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Risk Factors
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- polygenic risk score, cardiovascular disease, cardiovascular risk prediction, Framingham risk score, traditional cardiovascular risk factors, genetic susceptibility
- MeSH terms
- Cardiovascular Diseases, Humans, Phenotype, Predictive Value of Tests, Risk Factors, Genetic Variation, Biomarkers, Risk Assessment, Genome-Wide Association Study
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