title: Subgroups at high risk for ischaemic heart disease:identification and validation in 67 000 individuals from the general population.
abstract: BACKGROUND
  The aetiology of ischaemic heart disease (IHD) is complex and is influenced by a spectrum of environmental factors and susceptibility genes. Traditional statistical modelling considers such factors to act independently in an additive manner. The Patient Rule-Induction Method (PRIM) is a multi-model building strategy for evaluating risk attributable to context-dependent gene and environmental effects.
  
  
  METHODS
  PRIM was applied to 9073 participants from the prospective Copenhagen City Heart Study (CCHS). Gender-specific cumulative incidences were estimated for subgroups defined by categories of age, smoking, hypertension, diabetes, body mass index, total cholesterol, high-density lipoprotein cholesterol and triglycerides and by 94 single nucleotide variants (SNVs).Cumulative incidences for subgroups were validated using an independently ascertained sample of 58 240 participants from the Copenhagen General Population Study (CGPS).
  
  
  RESULTS
  In the CCHS the overall cumulative incidences were 0.17 in women and 0.21 in men. PRIM identified six and four mutually exclusive subgroups in women and men, respectively, with cumulative incidences of IHD ranging from 0.02 to 0.34. Cumulative incidences of IHD generated by PRIM in the CCHS were validated in four of the six subgroups of women and two of the four subgroups of men in the CGPS.
  
  
  CONCLUSIONS
  PRIM identified high-risk subgroups characterized by specific contexts of selected values of traditional risk factors and genetic variants. These subgroups were validated in an independently ascertained cohort study. Thus, a multi-model strategy may identify groups of individuals with substantially higher risk of IHD than the overall risk for the general population.
authors.affiliation: Department of Clinical Biochemistry, Rigshospitalet, The Copenhagen General Population Study, Herlev Hospital, The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen, Denmark, Department of Oncology, Wayne State University, Detroit, USA, Department of Clinical Biochemistry, Gentofte Hospital, Department of Clinical Biochemistry, Herlev Hospital, Copenhagen, Denmark, Department of Human Genetics, University of Michigan, Ann Arbor, USA and Copenhagen University Hospital and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Department of Clinical Biochemistry, Rigshospitalet, The Copenhagen General Population Study, Herlev Hospital, The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen, Denmark, Department of Oncology, Wayne State University, Detroit, USA, Department of Clinical Biochemistry, Gentofte Hospital, Department of Clinical Biochemistry, Herlev Hospital, Copenhagen, Denmark, Department of Human Genetics, University of Michigan, Ann Arbor, USA and Copenhagen University Hospital and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. ruth.frikke-schmidt@regionh.dk.
authors.forename: Ruth
authors.initials: R
authors.lastname: Frikke-Schmidt
authors.affiliation: Department of Clinical Biochemistry, Rigshospitalet, The Copenhagen General Population Study, Herlev Hospital, The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen, Denmark, Department of Oncology, Wayne State University, Detroit, USA, Department of Clinical Biochemistry, Gentofte Hospital, Department of Clinical Biochemistry, Herlev Hospital, Copenhagen, Denmark, Department of Human Genetics, University of Michigan, Ann Arbor, USA and Copenhagen University Hospital and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Department of Clinical Biochemistry, Rigshospitalet, The Copenhagen General Population Study, Herlev Hospital, The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen, Denmark, Department of Oncology, Wayne State University, Detroit, USA, Department of Clinical Biochemistry, Gentofte Hospital, Department of Clinical Biochemistry, Herlev Hospital, Copenhagen, Denmark, Department of Human Genetics, University of Michigan, Ann Arbor, USA and Copenhagen University Hospital and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Department of Clinical Biochemistry, Rigshospitalet, The Copenhagen General Population Study, Herlev Hospital, The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen, Denmark, Department of Oncology, Wayne State University, Detroit, USA, Department of Clinical Biochemistry, Gentofte Hospital, Department of Clinical Biochemistry, Herlev Hospital, Copenhagen, Denmark, Department of Human Genetics, University of Michigan, Ann Arbor, USA and Copenhagen University Hospital and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Anne
authors.initials: A
authors.lastname: Tybjærg-Hansen
authors.affiliation: Department of Clinical Biochemistry, Rigshospitalet, The Copenhagen General Population Study, Herlev Hospital, The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen, Denmark, Department of Oncology, Wayne State University, Detroit, USA, Department of Clinical Biochemistry, Gentofte Hospital, Department of Clinical Biochemistry, Herlev Hospital, Copenhagen, Denmark, Department of Human Genetics, University of Michigan, Ann Arbor, USA and Copenhagen University Hospital and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Greg
authors.initials: G
authors.lastname: Dyson
authors.affiliation: Department of Clinical Biochemistry, Rigshospitalet, The Copenhagen General Population Study, Herlev Hospital, The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen, Denmark, Department of Oncology, Wayne State University, Detroit, USA, Department of Clinical Biochemistry, Gentofte Hospital, Department of Clinical Biochemistry, Herlev Hospital, Copenhagen, Denmark, Department of Human Genetics, University of Michigan, Ann Arbor, USA and Copenhagen University Hospital and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Christiane L
authors.initials: CL
authors.lastname: Haase
authors.affiliation: Department of Clinical Biochemistry, Rigshospitalet, The Copenhagen General Population Study, Herlev Hospital, The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen, Denmark, Department of Oncology, Wayne State University, Detroit, USA, Department of Clinical Biochemistry, Gentofte Hospital, Department of Clinical Biochemistry, Herlev Hospital, Copenhagen, Denmark, Department of Human Genetics, University of Michigan, Ann Arbor, USA and Copenhagen University Hospital and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Marianne
authors.initials: M
authors.lastname: Benn
authors.affiliation: Department of Clinical Biochemistry, Rigshospitalet, The Copenhagen General Population Study, Herlev Hospital, The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen, Denmark, Department of Oncology, Wayne State University, Detroit, USA, Department of Clinical Biochemistry, Gentofte Hospital, Department of Clinical Biochemistry, Herlev Hospital, Copenhagen, Denmark, Department of Human Genetics, University of Michigan, Ann Arbor, USA and Copenhagen University Hospital and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Department of Clinical Biochemistry, Rigshospitalet, The Copenhagen General Population Study, Herlev Hospital, The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen, Denmark, Department of Oncology, Wayne State University, Detroit, USA, Department of Clinical Biochemistry, Gentofte Hospital, Department of Clinical Biochemistry, Herlev Hospital, Copenhagen, Denmark, Department of Human Genetics, University of Michigan, Ann Arbor, USA and Copenhagen University Hospital and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Department of Clinical Biochemistry, Rigshospitalet, The Copenhagen General Population Study, Herlev Hospital, The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen, Denmark, Department of Oncology, Wayne State University, Detroit, USA, Department of Clinical Biochemistry, Gentofte Hospital, Department of Clinical Biochemistry, Herlev Hospital, Copenhagen, Denmark, Department of Human Genetics, University of Michigan, Ann Arbor, USA and Copenhagen University Hospital and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Børge G
authors.initials: BG
authors.lastname: Nordestgaard
authors.affiliation: Department of Clinical Biochemistry, Rigshospitalet, The Copenhagen General Population Study, Herlev Hospital, The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen, Denmark, Department of Oncology, Wayne State University, Detroit, USA, Department of Clinical Biochemistry, Gentofte Hospital, Department of Clinical Biochemistry, Herlev Hospital, Copenhagen, Denmark, Department of Human Genetics, University of Michigan, Ann Arbor, USA and Copenhagen University Hospital and Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Charles F
authors.initials: CF
authors.lastname: Sing
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D003324:Coronary Artery Disease / Q000453:epidemiology / Q000235:genetics; D003718:Denmark / Q000453:epidemiology; D003920:Diabetes Mellitus / Q000453:epidemiology / Q000235:genetics; D004777:Environment; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000453:epidemiology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000453:epidemiology; D055815:Young Adult
chemical_list: D008055:Lipids
keywords: Cardiovascular disease; genetic epidemiology; risk factor