title: Incremental predictive value of 152 single nucleotide polymorphisms in the 10-year risk prediction of incident coronary heart disease: the Rotterdam Study.
abstract: OBJECTIVE
  To examine the incremental predictive value of genetic risk scores of coronary heart disease (CHD) in the 10-year risk prediction of incident CHD.
  
  
  METHODS
  In 5899 subjects, we used 152 single nucleotide polymorphisms (SNPs) associated with coronary artery disease by the CARDIoGRAMplusC4D consortium to construct three weighted genetic risk scores: (i) GRS(gws) based on 49 genome-wide significant SNPs; (ii) GRS(fdr) based on 103 suggestively associated SNPs; and (iii) GRS(all) based on all 152 SNPs. We examined the changes in discrimination and reclassification of incident CHD when adding the genetic risk scores to models including traditional risk factors. We repeated the analysis for prevalent CHD.
  
  
  RESULTS
  The genetic risk scores were associated with incident CHD despite adjustment for traditional risk factors and family history: participants had a 13% higher rate of CHD per standard deviation increase in GRS(all). GRS(all )improved the C-statistic by 0.006 [95% confidence interval (CI): 0.000, 0.013] beyond age and sex, 0.003 (95% CI: -0.001, 0.008) beyond traditional risk factors and 0.003 (95% CI: -0.001, 0.007) beyond traditional risk factors and family history. The genetic risk scores did not improve reclassification. GRS(all) strongly improved both discrimination and reclassification of prevalent CHD, even beyond traditional risk factors and family history, with a C-statistic improvement of 0.009 (0.003, 0.015).
  
  
  CONCLUSIONS
  Although the genetic risk scores based on 152 SNPs were associated with incident CHD, they did not improve risk prediction. This discrepancy may be the result of SNP discovery for prevalent rather than incident CHD, since the SNPs do improve prediction for prevalent disease.
authors.affiliation: Department of Epidemiology, and Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Paul S
authors.initials: PS
authors.lastname: de Vries
authors.affiliation: Department of Epidemiology, and Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Maryam
authors.initials: M
authors.lastname: Kavousi
authors.affiliation: Department of Epidemiology, and Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Symen
authors.initials: S
authors.lastname: Ligthart
authors.affiliation: Department of Epidemiology, and Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands Department of Epidemiology, and Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.affiliation: Department of Epidemiology, and Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.affiliation: Department of Epidemiology, and Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Oscar H
authors.initials: OH
authors.lastname: Franco
authors.affiliation: Department of Epidemiology, and Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands a.dehghan@erasmusmc.nl.
authors.forename: Abbas
authors.initials: A
authors.lastname: Dehghan
mesh_terms: D000368:Aged; D003324:Coronary Artery Disease / Q000235:genetics* / Q000401:mortality; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011446:Prospective Studies; D012307:Risk Factors
keywords: coronary heart disease; genetic risk scores; prediction; prevention