title: A genetic risk score is associated with incident cardiovascular disease and coronary artery calcium: the Framingham Heart Study.
abstract: 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.
  
  
  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.
authors.affiliation: Division of Cardiology and Clinical Epidemiology, McGill University Health Center and McGill University, Montreal, Quebec, Canada.
authors.forename: George
authors.initials: G
authors.lastname: Thanassoulis
authors.forename: Gina M
authors.initials: GM
authors.lastname: Peloso
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Pencina
authors.forename: Udo
authors.initials: U
authors.lastname: Hoffmann
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Fox
authors.forename: L Adrienne
authors.initials: LA
authors.lastname: Cupples
authors.forename: Daniel
authors.initials: D
authors.lastname: Levy
authors.forename: Ralph B
authors.initials: RB
authors.lastname: D'Agostino
authors.forename: Shih-Jen
authors.initials: SJ
authors.lastname: Hwang
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: O'Donnell
mesh_terms: D000328:Adult; D000483:Alleles; D002114:Calcinosis / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000235:genetics*; D002118:Calcium / Q000097:blood; D015331:Cohort Studies; D017023:Coronary Angiography; D003327:Coronary Disease / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D055106:Genome-Wide Association Study; D006801:Humans; D015994:Incidence; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012307:Risk Factors
chemical_list: D002118:Calcium