Ruth Frikke-Schmidt1, Anne Tybjærg-Hansen2, Greg Dyson3, Christiane L Haase3, Marianne Benn3, Børge G Nordestgaard2, Charles F Sing3. 1. 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. 2. 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. 3. 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.
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.
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: Ruth Frikke-Schmidt; Børge G Nordestgaard; Maria C A Stene; Amar A Sethi; Alan T Remaley; Peter Schnohr; Peer Grande; Anne Tybjaerg-Hansen Journal: JAMA Date: 2008-06-04 Impact factor: 56.272
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Authors: Jeppe Zacho; Anne Tybjaerg-Hansen; Jan Skov Jensen; Peer Grande; Henrik Sillesen; Børge G Nordestgaard Journal: N Engl J Med Date: 2008-10-30 Impact factor: 91.245
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Authors: Perciliz L Tan; Melanie E Garrett; Jason R Willer; Peter A Campochiaro; Betsy Campochiaro; Donald J Zack; Allison E Ashley-Koch; Nicholas Katsanis Journal: Invest Ophthalmol Vis Sci Date: 2017-03-01 Impact factor: 4.799