Multilocus Genetic Risk Scores for Coronary Heart Disease Prediction
Abstract
Objective—: Current guidelines do not support the use of genetic profiles in risk assessment of coronary heart disease (CHD). However, new single nucleotide polymorphisms associated with CHD and intermediate cardiovascular traits have recently been discovered. We aimed to compare several multilocus genetic risk score (MGRS) in terms of association with CHD and to evaluate clinical use. Approach and Results—: We investigated 6 Swedish prospective cohort studies with 10 612 participants free of CHD at baseline. We developed 1 overall MGRS based on 395 single nucleotide polymorphisms reported as being associated with cardiovascular traits, 1 CHD-specific MGRS, including 46 single nucleotide polymorphisms, and 6 trait-specific MGRS for each established CHD risk factors. Both the overall and the CHD-specific MGRS were significantly associated with CHD risk (781 incident events; hazard ratios for fourth versus first quartile, 1.54 and 1.52; P <0.001) and improved risk classification beyond established risk factors (net reclassification improvement, 4.2% and 4.9%; P =0.006 and 0.017). Discrimination improvement was modest (C-index improvement, 0.004). A polygene MGRS performed worse than the CHD-specific MGRS. We estimate that 1 additional CHD event for every 318 people screened at intermediate risk could be saved by measuring the CHD-specific genetic score in addition to the established risk factors. Conclusions—: Our results indicate that genetic information could be of some clinical value for prediction of CHD, although further studies are needed to address aspects, such as feasibility, ethics, and cost efficiency of genetic profiling in the primary prevention setting.
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When aggregated into a polygenic risk score, these risk alleles predict incident coronary events and give a continuous quantitative measure of genetic susceptibility.
“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 [21]
A polygenic risk score has robust associations with incident coronary events.
“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 [21]
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- Authors
- Ganna, A., Magnusson, P. K. E., Pedersen, N. L., de Faire, U., Reilly, M., Ärnlöv, J., Sundström, J., Hamsten, A., & Ingelsson, E.
- Affiliations
- Centre for Human Genetics (GB)
- From the Department of Medical Epidemiology and Biostatistics (A.G., P.K.E.M., N.L.P., M.R.), Division of Cardiovascular Epidemiology, Institute of Environmental Medicine (U.d.F.), Cardiovascular Genetics and Genomics Group, Atherosclerosis Research Unit, Department of Medicine Solna (A.H.), Karolinska Institutet, Stockholm, Sweden; Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory (A.G., J.Ä., E.I.) and Department of Medical Sciences, Cardiovascular Epidemiology...
- Science for Life Laboratory (SE)
- ORCID
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2013-09
- Volume
- 33
- Issue
- 9
- Pages
- 2267-2272
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W2121435580
- Cited by
- 156
- References
- 26
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 10 · 2023: 13 · 2022: 12 · 2021: 9 · 2020: 4 · 2019: 7 · 2018: 20 · 2017: 25 · 2016: 21 · 2015: 17 · 2014: 10 · 2013: 2 · 2012: 1
- FWCI
- 11.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- National Institute on Aging (R01AG004563, AG-10175, AG04563, AG 08724, AG028555, R01AG028555, AG 08861, R01AG010175, R01AG008724)
- National Human Genome Research Institute
- National Institute of Diabetes and Digestive and Kidney Diseases (DK066134, U01DK066134)
- 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 › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- coronary artery disease, single nucleotide polymorphisms, genetic risk prediction, cardiovascular traits, polygenic risk score, risk reclassification, primary prevention, intermediate cardiovascular risk
- MeSH terms
- Aged, Coronary Disease, Female, Genetic Testing, Humans, Longitudinal Studies, Male, Mass Screening, Middle Aged, Phenotype, Predictive Value of Tests, Prospective Studies, Registries, Risk Factors, Sweden, Time Factors, Incidence, Discriminant Analysis, Linear Models, Logistic Models, Proportional Hazards Models, Molecular Epidemiology, Risk Assessment, Disease-Free Survival, Quantitative Trait, Heritable, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Heredity
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