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A genetic risk score is associated with incident cardiovascular disease and coronary artery calcium: the Framingham Heart Study.

Publication ,  Journal Article
Thanassoulis, G; Peloso, GM; Pencina, MJ; Hoffmann, U; Fox, CS; Cupples, LA; Levy, D; D'Agostino, RB; Hwang, S-J; O'Donnell, CJ
Published in: Circ Cardiovasc Genet
February 1, 2012

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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Published In

Circ Cardiovasc Genet

DOI

EISSN

1942-3268

Publication Date

February 1, 2012

Volume

5

Issue

1

Start / End Page

113 / 121

Location

United States

Related Subject Headings

  • Risk Factors
  • Proportional Hazards Models
  • Predictive Value of Tests
  • Polymorphism, Single Nucleotide
  • Odds Ratio
  • Middle Aged
  • Male
  • Longitudinal Studies
  • Incidence
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
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Thanassoulis, G., Peloso, G. M., Pencina, M. J., Hoffmann, U., Fox, C. S., Cupples, L. A., … O’Donnell, C. J. (2012). A genetic risk score is associated with incident cardiovascular disease and coronary artery calcium: the Framingham Heart Study. Circ Cardiovasc Genet, 5(1), 113–121. https://doi.org/10.1161/CIRCGENETICS.111.961342
Thanassoulis, George, Gina M. Peloso, Michael J. Pencina, Udo Hoffmann, Caroline S. Fox, L Adrienne Cupples, Daniel Levy, Ralph B. D’Agostino, Shih-Jen Hwang, and Christopher J. O’Donnell. “A genetic risk score is associated with incident cardiovascular disease and coronary artery calcium: the Framingham Heart Study.Circ Cardiovasc Genet 5, no. 1 (February 1, 2012): 113–21. https://doi.org/10.1161/CIRCGENETICS.111.961342.
Thanassoulis G, Peloso GM, Pencina MJ, Hoffmann U, Fox CS, Cupples LA, et al. A genetic risk score is associated with incident cardiovascular disease and coronary artery calcium: the Framingham Heart Study. Circ Cardiovasc Genet. 2012 Feb 1;5(1):113–21.
Thanassoulis, George, et al. “A genetic risk score is associated with incident cardiovascular disease and coronary artery calcium: the Framingham Heart Study.Circ Cardiovasc Genet, vol. 5, no. 1, Feb. 2012, pp. 113–21. Pubmed, doi:10.1161/CIRCGENETICS.111.961342.
Thanassoulis G, Peloso GM, Pencina MJ, Hoffmann U, Fox CS, Cupples LA, Levy D, D’Agostino RB, Hwang S-J, O’Donnell CJ. A genetic risk score is associated with incident cardiovascular disease and coronary artery calcium: the Framingham Heart Study. Circ Cardiovasc Genet. 2012 Feb 1;5(1):113–121.

Published In

Circ Cardiovasc Genet

DOI

EISSN

1942-3268

Publication Date

February 1, 2012

Volume

5

Issue

1

Start / End Page

113 / 121

Location

United States

Related Subject Headings

  • Risk Factors
  • Proportional Hazards Models
  • Predictive Value of Tests
  • Polymorphism, Single Nucleotide
  • Odds Ratio
  • Middle Aged
  • Male
  • Longitudinal Studies
  • Incidence
  • Humans