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Cited by 267Lipoproteins and Cardiovascular HealthGenetic Associations and EpidemiologyNutrition, Genetics, and Disease

Incorporating a Genetic Risk Score Into Coronary Heart Disease Risk Estimates: Effect on Low-Density Lipoprotein Cholesterol Levels (the MI-GENES Clinical Trial)

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Kullo, Iftikhar J., Jouni, Hayan, Austin, Erin E., Brown, Sherry-Ann, Kruisselbrink, Teresa M., Isseh, Iyad N., Haddad, Raad A., Marroush, Tariq S. +7 more·2016·Circulation
DOI 10.1161/circulationaha.115.020109PMC PMC4803581
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Abstract

Background—: Whether knowledge of genetic risk for coronary heart disease (CHD) affects health-related outcomes is unknown. We investigated whether incorporating a genetic risk score (GRS) in CHD risk estimates lowers low-density lipoprotein cholesterol (LDL-C) levels. Methods and Results—: Participants (n=203, 45–65 years of age, at intermediate risk for CHD, and not on statins) were randomly assigned to receive their 10-year probability of CHD based either on a conventional risk score (CRS) or CRS + GRS ( + GRS). Participants in the + GRS group were stratified as having high or average/low GRS. Risk was disclosed by a genetic counselor followed by shared decision making regarding statin therapy with a physician. We compared the primary end point of LDL-C levels at 6 months and assessed whether any differences were attributable to changes in dietary fat intake, physical activity levels, or statin use. Participants (mean age, 59.4±5 years; 48% men; mean 10-year CHD risk, 8.5±4.1%) were allocated to receive either CRS (n=100) or + GRS (n=103). At the end of the study period, the + GRS group had a lower LDL-C than the CRS group (96.5±32.7 versus 105.9±33.3 mg/dL; P =0.04). Participants with high GRS had lower LDL-C levels (92.3±32.9 mg/dL) than CRS participants ( P =0.02) but not participants with low GRS (100.9±32.2 mg/dL; P =0.18). Statins were initiated more often in the + GRS group than in the CRS group (39% versus 22%, P <0.01). No significant differences in dietary fat intake and physical activity levels were noted. Conclusions—: Disclosure of CHD risk estimates that incorporated genetic risk information led to lower LDL-C levels than disclosure of CHD risk based on conventional risk factors alone. Clinical Trial Registration—: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01936675.

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  • Integrated models of PRS together with other lifestyle and clinical factors have enabled clinicians to more accurately quantify the risk of heart attack.

    “Additionally, integrated models of PRS together with other lifestyle and clinical factors have enabled clinicians to more accurately quantify the risk of heart attack for patients;”

    From Clinical use of current polygenic risk scores may exacerbate health disparities (2019) · cites this paper as [6]

    Methods > Study Design describes combining a genetic risk score with a conventional score to estimate 10-year coronary heart disease risk. But Discussion says the genetic score was not prospectively validated and presents refinement of risk estimates as a future possibility. The paper therefore does not establish that the combined model quantified heart-attack risk more accurately, or that lifestyle measures were included in the model. (LLM, conf=0.88)

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  • A polygenic burden of LDL-increasing SNPs can confer monogenic-equivalent risk of cardiovascular disease, with polygenic scores improving clinical models for risk assessment and statin prescription that can reduce coronary heart disease and improve healthcare delivery efficiency.

    “This enthusiasm is driven by observations that a polygenic burden of LDL-increasing SNPs can confer monogenic-equivalent risk of cardiovascular disease, with polygenic scores improving clinical models for risk assessment and statin prescription that can reduce coronary heart disease and improve healthcare delivery efficiency5–7.”

    From Clinical use of current polygenic risk scores may exacerbate health disparities (2019) · cites this paper as [6]

    Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

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  • Polygenic scores have contributed new approaches to risk prediction for adverse phenotypes related to heart disease.

    “For example, they have contributed new approaches to risk prediction for adverse phenotypes related to heart disease [21–23].”

    From Interpreting polygenic scores, polygenic adaptation, and human phenotypic differences (2019) · cites this paper as [21]

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Authors
Kullo, I. J., Jouni, H., Austin, E. E., Brown, S.-A., Kruisselbrink, T. M., Isseh, I. N., Haddad, R. A., Marroush, T. S., Shameer, K., Olson, J. E., Broeckel, U., Green, R. C., Schaid, D. J., Montori, V. M., & Bailey, K. R.
Affiliations
  • Brigham and Women's Hospital (US)
  • From the Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, MN (I.J.K., H.J., E.E.A., S.-A.B., T.M.K., I.N.I., R.A.H., T.S.M., K.S.); Department of Health Sciences Research, Mayo Clinic, Rochester, MN (J.E.O., D.J.S., K.R.B.); Department of Pediatrics, Medicine and Physiology, Medical College of Wisconsin, Milwaukee (U.B.); Division of Genetics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA (R.C.G.); and Knowledge and...
ORCID
Venue
Circulation
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2016-03-22
Volume
133
Issue
12
Pages
1181-1188
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
DOI
10.1161/circulationaha.115.020109
PMC
PMC4803581
OpenAlex
W2303883198
Cited by
267
References
9
Citations by year
2026: 24 · 2025: 26 · 2024: 23 · 2023: 27 · 2022: 32 · 2021: 28 · 2020: 29 · 2019: 16 · 2018: 26 · 2017: 25 · 2016: 11
FWCI
29.17
Type
journal article
Language
en
Open access
Locations
  • Circulation (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (UL1TR000135)
  • National Human Genome Research Institute (U01HG006379, U01HG004599, HG006500, HG04599, HG006379, U01HG006500)
  • National Center for Advancing Translational Sciences
Topics
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Nutrition, Genetics, and Disease
Keywords
polygenic risk score, coronary heart disease risk, LDL cholesterol, risk disclosure, shared decision-making, statin therapy, genetic counseling, intermediate cardiovascular risk, dietary fat intake, physical activity, risk communication
MeSH terms
Aged, Anxiety, Coronary Disease, Decision Making, Dietary Fats, Female, Follow-Up Studies, Genetic Counseling, Genotype, Humans, Cholesterol, LDL, Male, Middle Aged, Minnesota, Motor Activity, Patient Participation, Physician-Patient Relations, Probability, Risk Factors, Comorbidity, Risk Assessment, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide

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