Genetic contributions to variation in general cognitive function: a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53949).

Autor: 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, Haukeland University Hospital, Bergen, Norway., 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, Haukeland University Hospital, Bergen, Norway., 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 Brain Institute, The University of Queensland, Brisbane, QLD, Australia., 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 Sequencing Center, Baylor College of Medicine, Houston, TX, USA., 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, Finland., 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, Norway., Faul JD; Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA., Ford I; Robertson Center for Biostatistics, Glasgow, UK., Gottesman RF; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Griswold ME; Center of Biostatistics and Bioinformatics, University of Mississippi Medical Center, Jackson, MS, USA., Gudnason V; 1] Icelandic Heart Association, Kopavogur, Iceland [2] University of Iceland, Reykjavik, Iceland., Harris TB; Intramural Research Program National Institutes on Aging, National Institutes of Health, Bethesda, MD, USA., Heiss G; Department of Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill, NC, USA., Hofman A; 1] Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands [2] Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands., Holliday EG; Hunter Medical Research Institute and Faculty of Health, University of Newcastle, Newcastle, NSW, Australia., Huffman J; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK., Kardia SL; Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA., Kochan N; 1] Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, NSW, Australia [2] Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, NSW, Australia., Knopman DS; Department of Neurology, Mayo Clinic, Rochester, MN, USA., Kwok JB; 1] Neuroscience Research Australia, Randwick, NSW, Australia [2] School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia., Lambert JC; Inserm-UMR744, Institut Pasteur de Lille, Unité d'Epidémiologie et de Santé Publique, Lille, France., Lee T; 1] Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, NSW, Australia [2] Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, NSW, Australia., Li G; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA., Li SC; 1] Max Planck Institute for Human Development, Berlin, Germany [2] Technische Universität Dresden, Dresden, Germany., Loitfelder M; Department of Neurology, Medical University of Graz, Graz, Austria., Lopez OL; Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA., Lundervold AJ; 1] Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway [2] Kavli Research Centre for Aging and Dementia, Haraldsplass Deaconess Hospital, Bergen, Norway [3] K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, University of Bergen, Bergen, Norway., Lundqvist A; Umeå Center for Functional Brain Imaging (UFBI), Umeå University, Umeå, Sweden., Mather KA; Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, NSW, Australia., Mirza SS; 1] Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands [2] Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands., Nyberg L; 1] Umeå Center for Functional Brain Imaging (UFBI), Umeå University, Umeå, Sweden [2] Department of Radiation Sciences, Umeå University, Umeå, Sweden [3] Department of Integrative Medical Biology, Umeå University, Umeå, Sweden., Oostra BA; Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands., Palotie A; 1] Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK [2] Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland [3] Department of Medical Genetics, University of Helsinki and University Central Hospital, Helsinki, Finland., Papenberg G; 1] Max Planck Institute for Human Development, Berlin, Germany [2] Karolinska Institutet, Aging Research Center, Stockholm University, Stockholm, Sweden., Pattie A; Department of Psychology, University of Edinburgh, Edinburgh, UK., Petrovic K; Department of Neurology, Medical University of Graz, Graz, Austria., Polasek O; Faculty of Medicine, Department of Public Health, University of Split, Split, Croatia., Psaty BM; 1] Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA [2] Deparment of Epidemiology, University of Washington, Seattle, WA, USA [3] Deparment of Health Services, University of Washington, Seattle, WA, USA [4] Group Health Research Unit, Group Health Cooperative, Seattle, WA, USA., Redmond P; Department of Psychology, University of Edinburgh, Edinburgh, UK., Reppermund S; Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, NSW, Australia., Rotter JI; 1] Institute for Translational Genomics and Population Sciences Los Angeles BioMedical Research Institute, Harbor-UCLA Medical Center, Los Angeles, CA, USA [2] Division of Genetic Outcomes, Department of Pediatrics, Harbor-UCLA Medical Center, Los Angeles, CA, USA., Schmidt H; 1] Department of Neurology, Medical University of Graz, Graz, Austria [2] Centre for Molecular Medicine, Institute of Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria., Schuur M; 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., Schofield PW; School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia., Scott RJ; Hunter Medical Research Institute and Faculty of Health, University of Newcastle, Newcastle, NSW, Australia., Steen VM; 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, Haukeland University Hospital, Bergen, Norway., Stott DJ; Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK., van Swieten JC; Department of Neurology, Erasmus University Medical Center, Rotterdam, The Netherlands., Taylor KD; 1] Institute for Translational Genomics and Population Sciences Los Angeles BioMedical Research Institute, Harbor-UCLA Medical Center, Los Angeles, CA, USA [2] Department of Pediatrics, Harbor-UCLA Medical Center, Los Angeles, CA, USA., Trollor J; 1] Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, NSW, Australia [2] Department of Developmental Disability Neuropsychiatry, School of Psychiatry, University of New South Wales, Sydney, NSW, Australia., Trompet S; 1] Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands [2] Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands., Uitterlinden AG; 1] Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands [2] Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands [3] Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands., Weinstein G; 1] Department of Neurology, Boston University School of Medicine, Boston, MA, USA [2] Framingham Heart Study, Framingham, MA, USA., Widen E; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland., Windham BG; Division of Geriatrics, Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA., Jukema JW; 1] Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands [2] Durrer Center for Cardiogenetic Research, Amsterdam, The Netherlands [3] Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands., Wright AF; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK., Wright MJ; Neuroimaging Genetics Group, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia., Yang Q; 1] Framingham Heart Study, Framingham, MA, USA [2] Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA., Amieva H; Inserm U897, Université Bordeaux Segalen, Bordeaux, France., Attia JR; Hunter Medical Research Institute and Faculty of Health, University of Newcastle, Newcastle, NSW, Australia., Bennett DA; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA., Brodaty H; 1] Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, NSW, Australia [2] Dementia Collaborative Research Centre, University of New South Wales, Sydney, NSW, Australia., de Craen AJ; 1] Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands [2] Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands., Hayward C; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK., Ikram MA; 1] Department of Neurology, Erasmus University Medical Center, Rotterdam, The Netherlands [2] Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands [3] Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands [4] Department of Radiology, Erasmus University Medical Center, Rotterdam, The Netherlands., Lindenberger U; Max Planck Institute for Human Development, Berlin, Germany., Nilsson LG; ARC, Karolinska Institutet, Stockholm and UFBI, Umeå University, Umeå, Sweden., Porteous DJ; 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] Generation Scotland, University of Edinburgh Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK., Räikkönen K; Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland., Reinvang I; Department of Psychology, University of Oslo, Oslo, Norway., Rudan I; Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK., Sachdev PS; 1] Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, NSW, Australia [2] Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, NSW, Australia., Schmidt R; Department of Neurology, Medical University of Graz, Graz, Austria., Schofield PR; 1] Neuroscience Research Australia, Sydney, NSW, Australia [2] Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia., Srikanth V; 1] Menzies Research Institute, Hobart, Tasmania [2] Stroke and Ageing Research, Medicine, Southern Clinical School, Monash University, Melbourne, VIC, Australia., Starr JM; 1] Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK [2] Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK., Turner ST; Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA., Weir DR; Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA., Wilson JF; Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK., van Duijn C; 1] Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands [2] Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands., Launer L; Intramural Research Program National Institutes on Aging, National Institutes of Health, Bethesda, MD, USA., Fitzpatrick AL; 1] Deparment of Epidemiology, University of Washington, Seattle, WA, USA [2] Department of Global Health, University of Washington, Seattle, WA, USA., Seshadri S; 1] Department of Neurology, Boston University School of Medicine, Boston, MA, USA [2] Framingham Heart Study, Framingham, MA, USA., Mosley TH Jr; Division of Geriatrics, Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA., Deary IJ; 1] Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK [2] Department of Psychology, University of Edinburgh, Edinburgh, UK.
Jazyk: angličtina
Zdroj: Molecular psychiatry [Mol Psychiatry] 2015 Feb; Vol. 20 (2), pp. 183-92. Date of Electronic Publication: 2015 Feb 03.
DOI: 10.1038/mp.2014.188
Abstrakt: 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.
Databáze: MEDLINE