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A Genetic Risk Score Is Associated With Incident Cardiovascular Disease and Coronary Artery Calcium: The Framingham Heart Study
Open accessAbstract
Background—: Limited data exist regarding the use of a genetic risk score (GRS) for predicting risk of incident cardiovascular disease (CVD) in US-based samples. Methods and Results—: By using findings from recent genome-wide association studies, we constructed GRSs composed of 13 genetic variants associated with myocardial infarction or other manifestations of coronary heart disease (CHD) and 102 genetic variants associated with CHD or its major risk factors. We also updated the 13 single-nucleotide polymorphism (SNP) GRSs with 16 SNPs recently discovered by genome-wide association studies. We estimated the association, discrimination, and risk reclassification of each GRS for incident cardiovascular events and prevalent coronary artery calcium (CAC). In analyses adjusted for age, sex, CVD risk factors, and parental history of CVD, the 13 SNP GRSs were significantly associated with incident hard CHD (hazard ratio, 1.07; 95% CI, 1.00–1.15; P =0.04), CVD (hazard ratio per allele, 1.05; 95% CI, 1.01–1.09; P =0.03), and high CAC (defined as >75 th age- and sex-specific percentile; odds ratio per allele, 1.18; 95% CI, 1.11–1.26; P =3.4×10 −7 ). The GRS did not improve discrimination for incident CHD or CVD but led to modest improvements in risk reclassification. However, significant improvements in discrimination and risk reclassification were observed for the prediction of high CAC. The addition of 16 newly discovered SNPs to the 13 SNP GRSs did not significantly modify these results. Conclusions—: A GRS composed of 13 SNPs associated with coronary disease is an independent predictor of cardiovascular events and of high CAC, modestly improves risk reclassification for incident CHD, and significantly improves discrimination for high CAC. The addition of recently discovered SNPs did not significantly improve the performance of this GRS.
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“The CT coronary calcium score is a measure of the burden of coronary atherosclerosis and is one of the most widely accepted measures of cardiovascular risk5,6.”
From Deep convolutional neural networks to predict cardiovascular risk from computed tomography (2021) · cites this paper as [6]
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In the citing paper
“The CAC score was measured manually by expert readers using the method by Agatston and Janowitz5,6 on dedicated workstations, as reported in the parent FHS17, PROMISE19, and ROMICAT-II20 studies.”
From Deep convolutional neural networks to predict cardiovascular risk from computed tomography (2021) · cites this paper as [6]
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In the citing paper
“Coronary artery calcium is an accurate predictor of cardiovascular events.”
From Deep convolutional neural networks to predict cardiovascular risk from computed tomography (2021) · cites this paper as [6]
Experimental — accuracy not yet measuredIn the citing paper
“Our finding that a polygenic risk score has robust associations with incident coronary events is well aligned with previous studies of both primary and secondary prevention populations.16–24”
From Genetic Risk, Adherence to a Healthy Lifestyle, and Coronary Disease (2016) · cites this paper as [19]
In the citing paper
“These risk alleles, when aggregated into a polygenic risk score, are predictive of incident coronary events and provide a continuous and quantitative measure of genetic susceptibility.16–24”
From Genetic Risk, Adherence to a Healthy Lifestyle, and Coronary Disease (2016) · cites this paper as [19]
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Metadata
- Authors
- Thanassoulis, G., Peloso, G. M., Pencina, M. J., Hoffmann, U., Fox, C. S., Cupples, L. A., Levy, D., D'Agostino, R. B., Hwang, S.-J., & O'Donnell, C. J.
- Affiliations
- Boston University (US)
- From the Division of Cardiology and Clinical Epidemiology, McGill University Health Center and McGill University, Montreal, Quebec, Canada (G.T.); National Heart, Lung and Blood Institute (NHLBI) of the National Institutes of Health (NIH) Framingham Heart Study, Framingham, MA (G.T., G.M.P., M.J.P., C.S.F., L.A.C., D.L., R.B.D.'A., S.-J.H., C.J.O.); School of Medicine (G.T.) and Department of Mathematics (M.J.P., R.B.D.'A.), Boston University, Boston, MA; Center for Population Studies, NHLBI...
- ORCID
- Venue
- Circulation: Cardiovascular Genetics
- Published
- 2012-02
- Volume
- 5
- Issue
- 1
- Pages
- 113-121
- ISSN
- 1942-325X (ISSN-L)
- 1942-3268
- PMC
- PMC3292865
- OpenAlex
- W2135313485
- Cited by
- 211
- References
- 73
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 5 · 2023: 3 · 2022: 7 · 2021: 13 · 2020: 10 · 2019: 10 · 2018: 15 · 2017: 27 · 2016: 18 · 2015: 31 · 2014: 20 · 2013: 28 · 2012: 18
- FWCI
- 18.70
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Circulation Cardiovascular Genetics (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (Z99 HL999999, n01hc25195-41-0-1, n02hl64278-6-0-0)
- Canadian Institutes of Health Research
- National Heart, Lung, and Blood Institute (N01‐HC25195, ZIAHL006002, N02- HL-64278, N01-HC-025195, Z01HL006002)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Nutrition, Genetics, and Disease
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Risk Factors
- Keywords
- polygenic risk score, cardiovascular disease, coronary artery calcium, coronary artery disease, myocardial infarction, single nucleotide polymorphisms, risk reclassification, discrimination (statistics), incident cardiovascular events, genetic variants
- MeSH terms
- Adult, Alleles, Calcinosis, Calcium, Coronary Disease, Female, Follow-Up Studies, Humans, Longitudinal Studies, Male, Middle Aged, Predictive Value of Tests, Risk Factors, Cohort Studies, Incidence, Proportional Hazards Models, Odds Ratio, Coronary Angiography, Polymorphism, Single Nucleotide, Genome-Wide Association Study
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