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Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53949).
Davies, G; Armstrong, N; Bis, J C; Bressler, J; Chouraki, V; Giddaluru, S; Hofer, E; Ibrahim-Verbaas, C A; Kirin, M; Lahti, J; van der Lee, S J; Le Hellard, S; Liu, T; Marioni, R E; Oldmeadow, C; Postmus, I; Smith, A V; Smith, J A; Thalamuthu, A; Thomson, R; Vitart, V; Wang, J; Yu, L; Zgaga, L; Zhao, W; Boxall, R; Harris, S E; Hill, W D; Liewald, D C; Luciano, M; Adams, H; Ames, D; Amin, N; Amouyel, P; Assareh, A A; Au, R; Becker, J T; Beiser, A; Berr, C; Bertram, L; Boerwinkle, E; Buckley, B M; Campbell, H; Corley, J; De Jager, P L; Dufouil, C; Eriksson, J G; Espeseth, T; Faul, J D; Ford, I.
Afiliação
  • Davies G; 1] Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK [2] Department of Psychology, University of Edinburgh, Edinburgh, UK.
  • Armstrong N; School of Mathematics and Statistics, University of Sydney, Sydney, NSW, Australia.
  • Bis JC; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
  • Bressler J; Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA.
  • Chouraki V; 1] Inserm-UMR744, Institut Pasteur de Lille, Unité d'Epidémiologie et de Santé Publique, Lille, France [2] Department of Neurology, Boston University School of Medicine, Boston, MA, USA.
  • Giddaluru S; 1] K.G. Jebsen Centre for Psychosis Research and the Norwegian Centre for Mental Disorders Research (NORMENT), Department of Clinical Science, University of Bergen, Bergen, Norway [2] Dr Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Hauke
  • Hofer E; 1] Department of Neurology, Medical University of Graz, Graz, Austria [2] Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria.
  • Ibrahim-Verbaas CA; 1] Department of Neurology, Erasmus University Medical Center, Rotterdam, The Netherlands [2] Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
  • Kirin M; Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.
  • Lahti J; 1] Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland [2] Folkhälsan Research Centre, Helsinki, Finland.
  • van der Lee SJ; Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
  • Le Hellard S; 1] K.G. Jebsen Centre for Psychosis Research and the Norwegian Centre for Mental Disorders Research (NORMENT), Department of Clinical Science, University of Bergen, Bergen, Norway [2] Dr Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Hauke
  • Liu T; 1] Max Planck Institute for Human Development, Berlin, Germany [2] Max Planck Institute for Molecular Genetics, Berlin, Germany.
  • Marioni RE; 1] Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK [2] Medical Genetics Section, University of Edinburgh Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK [3] Queensland B
  • Oldmeadow C; Hunter Medical Research Institute and Faculty of Health, University of Newcastle, Newcastle, NSW, Australia.
  • Postmus I; 1] Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands [2] Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands.
  • Smith AV; 1] Icelandic Heart Association, Kopavogur, Iceland [2] University of Iceland, Reykjavik, Iceland.
  • Smith JA; Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA.
  • Thalamuthu A; Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
  • Thomson R; Menzies Research Institute, Hobart, Tasmania.
  • Vitart V; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
  • Wang J; 1] Framingham Heart Study, Framingham, MA, USA [2] Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
  • Yu L; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
  • Zgaga L; 1] Department of Public Health and Primary Care, Trinity College Dublin, Dublin, Ireland [2] Andrija Stampar School of Public Health, Medical School, University of Zagreb, Zagreb, Croatia.
  • Zhao W; Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA.
  • Boxall R; Medical Genetics Section, University of Edinburgh Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK.
  • Harris SE; 1] Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK [2] Medical Genetics Section, University of Edinburgh Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK.
  • Hill WD; Department of Psychology, University of Edinburgh, Edinburgh, UK.
  • Liewald DC; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
  • Luciano M; 1] Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK [2] Department of Psychology, University of Edinburgh, Edinburgh, UK.
  • Adams H; 1] Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands [2] Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands.
  • Ames D; 1] National Ageing Research Institute, Royal Melbourne Hospital, Melbourne, VIC, Australia [2] Academic Unit for Psychiatry of Old Age, St George's Hospital, University of Melbourne, Kew, Australia.
  • Amin N; 1] Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands [2] Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands.
  • Amouyel P; Inserm-UMR744, Institut Pasteur de Lille, Unité d'Epidémiologie et de Santé Publique, Lille, France.
  • Assareh AA; Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
  • Au R; 1] Department of Neurology, Boston University School of Medicine, Boston, MA, USA [2] Framingham Heart Study, Framingham, MA, USA.
  • Becker JT; 1] Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA [2] Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA [3] Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA.
  • Beiser A; 1] Department of Neurology, Boston University School of Medicine, Boston, MA, USA [2] Framingham Heart Study, Framingham, MA, USA.
  • Berr C; 1] Inserm, U106, Montpellier, France [2] Université Montpellier I, Montpellier, France.
  • Bertram L; 1] Max Planck Institute for Molecular Genetics, Berlin, Germany [2] Faculty of Medicine, School of Public Health, Imperial College, London, UK.
  • Boerwinkle E; 1] Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA [2] Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center at Houston, Houston, TX, USA [3] Human Genome
  • Buckley BM; Department of Pharmacology and Therapeutics, University College Cork, Cork, Ireland.
  • Campbell H; Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.
  • Corley J; Department of Psychology, University of Edinburgh, Edinburgh, UK.
  • De Jager PL; 1] Program in Translational NeuroPsychiatric Genomics, Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA [2] Harvard Medical School, Boston, MA, USA [3] Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
  • Dufouil C; 1] Inserm U708, Neuroepidemiology, Paris, France [2] Inserm U897, Université Bordeaux Segalen, Bordeaux, France.
  • Eriksson JG; 1] Folkhälsan Research Centre, Helsinki, Finland [2] National Institute for Health and Welfare, Helsinki, Finland [3] Department of General Practice and Primary health Care, University of Helsinki, Helsinki, Finland [4] Unit of General Practice, Helsinki University Central Hospital, Helsinki, Finlan
  • Espeseth T; 1] K.G. Jebsen Centre for Psychosis Research, Norwegian Centre For Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway [2] Department of Psychology, University of Oslo, Oslo, Norwa
  • Faul JD; Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA.
  • Ford I; Robertson Center for Biostatistics, Glasgow, UK.
Mol Psychiatry ; 20(2): 183-92, 2015 Feb.
Article em En | MEDLINE | ID: mdl-25644384
ABSTRACT
General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health- and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N=53,949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively rs10457441, P=3.93 × 10(-9), MIR2113; rs17522122, P=2.55 × 10(-8), AKAP6; rs10119, P=5.67 × 10(-9), APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P=1 × 10(-6)). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N=6617) and the Health and Retirement Study (N=5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e.=5%) and 28% (s.e.=7%), respectively. Using polygenic prediction analysis, ~1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N=5487; P=1.5 × 10(-17)). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease TOMM40, APOE, ABCG1 and MEF2C.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cognição / Transtornos Cognitivos / Predisposição Genética para Doença / Polimorfismo de Nucleotídeo Único / Proteína HMGN1 Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Aged / Aged80 / Female / Humans / Male / Middle aged País/Região como assunto: Europa Idioma: En Revista: Mol Psychiatry Assunto da revista: BIOLOGIA MOLECULAR / PSIQUIATRIA Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Reino Unido
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Cognição / Transtornos Cognitivos / Predisposição Genética para Doença / Polimorfismo de Nucleotídeo Único / Proteína HMGN1 Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Aged / Aged80 / Female / Humans / Male / Middle aged País/Região como assunto: Europa Idioma: En Revista: Mol Psychiatry Assunto da revista: BIOLOGIA MOLECULAR / PSIQUIATRIA Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Reino Unido