Genetic contributions to variation in general cognitive function: A meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949)

Research output: Contribution to journal › Research article › Contributed › peer-review

Contributors

  • G. Davies - , University of Edinburgh (Author)
  • N. Armstrong - , University of Sydney (Author)
  • J. C. Bis - , University of Washington (Author)
  • J. Bressler - , University of Texas Health Science Center at Houston (Author)
  • V. Chouraki - , Institut Pasteur de Lille, Boston University (Author)
  • S. Giddaluru - , University of Bergen (Author)
  • E. Hofer - , Medical University of Graz (Author)
  • C. A. Ibrahim-Verbaas - , Erasmus University Rotterdam (Author)
  • M. Kirin - , University of Edinburgh (Author)
  • J. Lahti - , University of Helsinki, Folkhalsan (Author)
  • S. J. Van Der Lee - , Erasmus University Rotterdam (Author)
  • S. Le Hellard - , University of Bergen (Author)
  • T. Liu - , Max Planck Institute for Human Development, Max Planck Institute for Molecular Genetics (Author)
  • R. E. Marioni - , University of Edinburgh, University of Queensland (Author)
  • C. Oldmeadow - , University of Newcastle (Author)
  • I. Postmus - , Leiden University, Netherlands Consortium for Healthy Ageing (Author)
  • A. V. Smith - , Icelandic Heart Association, University of Iceland (Author)
  • J. A. Smith - , University of Michigan, Ann Arbor (Author)
  • A. Thalamuthu - , University of New South Wales (Author)
  • R. Thomson - , University of Tasmania (Author)
  • V. Vitart - , University of Edinburgh (Author)
  • J. Wang - , National Institutes of Health (NIH), Boston University (Author)
  • L. Yu - , Rush University (Author)
  • L. Zgaga - , Trinity College Dublin, University of Zagreb (Author)
  • W. Zhao - , University of Michigan, Ann Arbor (Author)
  • R. Boxall - , University of Edinburgh (Author)
  • S. E. Harris - , University of Edinburgh (Author)
  • W. D. Hill - , University of Edinburgh (Author)
  • D. C. Liewald - , University of Edinburgh (Author)
  • M. Luciano - , University of Edinburgh (Author)
  • H. Adams - , Netherlands Consortium for Healthy Ageing, Erasmus University Rotterdam (Author)
  • D. Ames - , Royal Melbourne Hospital, University of Melbourne (Author)
  • N. Amin - , Erasmus University Rotterdam, Netherlands Consortium for Healthy Ageing (Author)
  • P. Amouyel - , Institut Pasteur de Lille (Author)
  • A. A. Assareh - , University of New South Wales (Author)
  • R. Au - , Boston University, National Institutes of Health (NIH) (Author)
  • J. T. Becker - , University of Pittsburgh (Author)
  • A. Beiser - , Boston University, National Institutes of Health (NIH) (Author)
  • C. Berr - , INSERM - Institut national de la santé et de la recherche médicale, University of Montpellier (Author)
  • L. Bertram - , Max Planck Institute for Molecular Genetics, Imperial College London (Author)
  • E. Boerwinkle - , University of Texas Health Science Center at Houston, Baylor College of Medicine (Author)
  • B. M. Buckley - , University College Cork (Author)
  • H. Campbell - , University of Edinburgh (Author)
  • J. Corley - , University of Edinburgh (Author)
  • P. L. De Jager - , Harvard University, Broad Institute of Harvard University and MIT (Author)
  • C. Dufouil - , INSERM - Institut national de la santé et de la recherche médicale (Author)
  • J. G. Eriksson - , Folkhalsan, National Institute for Health and Welfare, University of Helsinki (Author)
  • T. Espeseth - , University of Oslo (Author)
  • J. D. Faul - , University of Michigan, Ann Arbor (Author)
  • I. Ford - , University of Glasgow (Author)
  • Generation Scotland - , University of Edinburgh (Author)
  • R. F. Gottesman - , Johns Hopkins University (Author)
  • M. E. Griswold - , University of Mississippi (Author)
  • V. Gudnason - , Icelandic Heart Association, University of Iceland (Author)
  • T. B. Harris - , National Institutes of Health (NIH) (Author)
  • G. Heiss - , University of North Carolina at Chapel Hill (Author)
  • A. Hofman - , Netherlands Consortium for Healthy Ageing, Erasmus University Rotterdam (Author)
  • E. G. Holliday - , University of Newcastle (Author)
  • J. Huffman - , University of Edinburgh (Author)
  • S. L.R. Kardia - , University of Michigan, Ann Arbor (Author)
  • N. Kochan - , University of New South Wales, Prince of Wales Hospital (Author)
  • D. S. Knopman - , Mayo Clinic Rochester, MN (Author)
  • J. B. Kwok - , Neuroscience Research Australia, University of New South Wales (Author)
  • J. C. Lambert - , Institut Pasteur de Lille (Author)
  • T. Lee - , University of New South Wales, Prince of Wales Hospital (Author)
  • G. Li - , University of Washington (Author)
  • S. C. Li - , Chair of Lifespan Developmental Neuroscience, Max Planck Institute for Human Development (Author)
  • M. Loitfelder - , Medical University of Graz (Author)
  • O. L. Lopez - , University of Pittsburgh (Author)
  • A. J. Lundervold - , University of Bergen, Equinor ASA (Author)
  • A. Lundqvist - , Umeå University (Author)
  • K. A. Mather - , University of New South Wales (Author)
  • S. S. Mirza - , Netherlands Consortium for Healthy Ageing, Erasmus University Rotterdam (Author)
  • L. Nyberg - , Umeå University (Author)
  • B. A. Oostra - , Erasmus University Rotterdam (Author)
  • A. Palotie - , Wellcome Trust, University of Helsinki (Author)
  • G. Papenberg - , Max Planck Institute for Human Development, Stockholm University (Author)
  • A. Pattie - , University of Edinburgh (Author)
  • K. Petrovic - , Medical University of Graz (Author)
  • O. Polasek - , University of Split (Author)
  • B. M. Psaty - , University of Washington, Group Health Cooperative (Author)
  • P. Redmond - , University of Edinburgh (Author)
  • S. Reppermund - , University of New South Wales (Author)
  • J. I. Rotter - , University of California at Los Angeles (Author)
  • H. Schmidt - , Medical University of Graz (Author)
  • M. Schuur - , Erasmus University Rotterdam (Author)
  • P. W. Schofield - , University of Newcastle (Author)
  • R. J. Scott - , University of Newcastle (Author)
  • V. M. Steen - , University of Bergen (Author)
  • D. J. Stott - , University of Glasgow (Author)
  • J. C. Van Swieten - , Erasmus University Rotterdam (Author)
  • K. D. Taylor - , University of California at Los Angeles (Author)
  • J. Trollor - , University of New South Wales (Author)
  • S. Trompet - , Leiden University (Author)
  • A. G. Uitterlinden - , Netherlands Consortium for Healthy Ageing, Erasmus University Rotterdam (Author)
  • G. Weinstein - , Boston University, National Institutes of Health (NIH) (Author)
  • E. Widen - , University of Helsinki (Author)
  • B. G. Windham - , University of Mississippi (Author)
  • J. W. Jukema - , Leiden University, Durrer Center for Cardiogenetic Research, Royal Netherlands Academy of Arts and Sciences (Author)
  • A. F. Wright - , University of Edinburgh (Author)
  • M. J. Wright - , Queensland Institute of Medical Research (Author)
  • Q. Yang - , National Institutes of Health (NIH), Boston University (Author)
  • H. Amieva - , INSERM - Institut national de la santé et de la recherche médicale (Author)
  • J. R. Attia - , University of Newcastle (Author)
  • D. A. Bennett - , Rush University (Author)
  • H. Brodaty - , University of New South Wales (Author)
  • A. J.M. De Craen - , Leiden University, Netherlands Consortium for Healthy Ageing (Author)
  • C. Hayward - , University of Edinburgh (Author)
  • M. A. Ikram - , Erasmus University Rotterdam, Netherlands Consortium for Healthy Ageing (Author)
  • U. Lindenberger - , Max Planck Institute for Human Development (Author)
  • L. G. Nilsson - , Umeå University (Author)
  • D. J. Porteous - , University of Edinburgh (Author)
  • K. Räikkönen - , University of Helsinki (Author)
  • I. Reinvang - , University of Oslo (Author)
  • I. Rudan - , University of Edinburgh (Author)
  • P. S. Sachdev - , University of New South Wales, Prince of Wales Hospital (Author)
  • R. Schmidt - , Medical University of Graz (Author)
  • P. R. Schofield - , Neuroscience Research Australia, University of New South Wales (Author)
  • V. Srikanth - , University of Tasmania, Monash University (Author)
  • J. M. Starr - , University of Edinburgh (Author)
  • S. T. Turner - , Mayo Clinic Rochester, MN (Author)
  • D. R. Weir - , University of Michigan, Ann Arbor (Author)
  • J. F. Wilson - , University of Edinburgh (Author)
  • C. Van Duijn - , Erasmus University Rotterdam, Netherlands Consortium for Healthy Ageing (Author)
  • L. Launer - , National Institutes of Health (NIH) (Author)
  • A. L. Fitzpatrick - , University of Washington (Author)
  • S. Seshadri - , Boston University, National Institutes of Health (NIH) (Author)
  • T. H. Mosley - , University of Mississippi (Author)
  • I. J. Deary - , University of Edinburgh (Author)

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.

Details

Original languageEnglish
Pages (from-to)183-192
Number of pages10
JournalMolecular psychiatry
Volume20
Issue number2
Publication statusPublished - 1 Feb 2015
Peer-reviewedYes

External IDs

PubMed 25644384
ORCID /0000-0001-8409-5390/work/158767944

Keywords

Sustainable Development Goals

ASJC Scopus subject areas