title: Marginal role for 53 common genetic variants in cardiovascular disease prediction.
abstract: We investigated discrimination and calibration of cardiovascular disease (CVD) risk scores when genotypic was added to phenotypic information. The potential of genetic information for those at intermediate risk by a phenotype-based risk score was assessed.
  
  
  
  Data were from seven prospective studies including 11 851 individuals initially free of CVD or diabetes, with 1444 incident CVD events over 10 years' follow-up. We calculated a score from 53 CVD-related single nucleotide polymorphisms and an established CVD risk equation 'QRISK-2' comprising phenotypic measures. The area under the receiver operating characteristic curve (AUROC), detection rate for given false-positive rate (FPR) and net reclassification improvement (NRI) index were estimated for gene scores alone and in addition to the QRISK-2 CVD risk score. We also evaluated use of genetic information only for those at intermediate risk according to QRISK-2.
  
  
  
  The AUROC was 0.635 for QRISK-2 alone and 0.623 with addition of the gene score. The detection rate for 5% FPR improved from 11.9% to 12.0% when the gene score was added. For a 10-year CVD risk cut-off point of 10%, the NRI was 0.25% when the gene score was added to QRISK-2. Applying the genetic risk score only to those with QRISK-2 risk of 10%-<20% and prescribing statins where risk exceeded 20% suggested that genetic information could prevent one additional event for every 462 people screened.
  
  
  
  The gene score produced minimal incremental population-wide utility over phenotypic risk prediction of CVD. Tailored prediction using genetic information for those at intermediate risk may have clinical utility.
authors.affiliation: School of Social & Community Medicine, University of Bristol, Bristol, UK Department of Primary Care & Population Health, University College London, London, UK.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Morris
authors.affiliation: Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, UK.
authors.forename: Jackie A
authors.initials: JA
authors.lastname: Cooper
authors.affiliation: Institute of Cardiovascular Science and Farr Institute, University College London, London, UK.
authors.forename: Tina
authors.initials: T
authors.lastname: Shah
authors.affiliation: MRC Unit for Lifelong Health and Ageing at UCL, London, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Wong
authors.affiliation: Institute of Cardiovascular Science and Farr Institute, University College London, London, UK MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Fotios
authors.initials: F
authors.lastname: Drenos
authors.affiliation: Institute of Cardiovascular Science and Farr Institute, University College London, London, UK.
authors.forename: Jorgen
authors.initials: J
authors.lastname: Engmann
authors.affiliation: Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.
authors.forename: Stela
authors.initials: S
authors.lastname: McLachlan
authors.affiliation: Department of Primary Care & Population Health, University College London, London, UK.
authors.forename: Barbara
authors.initials: B
authors.lastname: Jefferis
authors.affiliation: Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Caroline
authors.initials: C
authors.lastname: Dale
authors.affiliation: MRC Unit for Lifelong Health and Ageing at UCL, London, UK.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Hardy
authors.affiliation: MRC Unit for Lifelong Health and Ageing at UCL, London, UK.
authors.forename: Diana
authors.initials: D
authors.lastname: Kuh
authors.affiliation: School of Social & Community Medicine, University of Bristol, Bristol, UK.
authors.forename: Yoav
authors.initials: Y
authors.lastname: Ben-Shlomo
authors.affiliation: Department of Primary Care & Population Health, University College London, London, UK.
authors.forename: S Goya
authors.initials: SG
authors.lastname: Wannamethee
authors.affiliation: Division of Population Health Sciences and Education, St George's, University of London, London, UK.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Whincup
authors.affiliation: Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, UK.
authors.forename: Juan-Pablo
authors.initials: JP
authors.lastname: Casas
authors.affiliation: Department of Epidemiology & Public Health, UCL Institute of Epidemiology & Health Care, University College London, London, UK.
authors.forename: Mika
authors.initials: M
authors.lastname: Kivimaki
authors.affiliation: Department of Epidemiology & Public Health, UCL Institute of Epidemiology & Health Care, University College London, London, UK Institute for Social and Economic Research, University of Essex, Colchester, UK.
authors.forename: Meena
authors.initials: M
authors.lastname: Kumari
authors.affiliation: Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, UK.
authors.forename: Philippa J
authors.initials: PJ
authors.lastname: Talmud
authors.affiliation: Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.
authors.forename: Jacqueline F
authors.initials: JF
authors.lastname: Price
authors.affiliation: Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: Frank
authors.initials: F
authors.lastname: Dudbridge
authors.affiliation: Institute of Cardiovascular Science and Farr Institute, University College London, London, UK.
authors.forename: Aroon D
authors.initials: AD
authors.lastname: Hingorani
authors.affiliation: Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, UK.
authors.forename: Steve E
authors.initials: SE
authors.lastname: Humphries
mesh_terms: D000328:Adult; D019540:Area Under Curve; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D005189:False Positive Reactions; D005260:Female; D020869:Gene Expression Profiling; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012372:ROC Curve; D015203:Reproducibility of Results; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D005819:Genetic Markers