Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
23358156
TITLE
Childhood intelligence is heritable, highly polygenic and associated with FNBP1L.
ABSTRACT
Intelligence in childhood, as measured by psychometric cognitive tests, is a strong predictor of many important life outcomes, including educational attainment, income, health and lifespan. Results from twin, family and adoption studies are consistent with general intelligence being highly heritable and genetically stable throughout the life course. No robustly associated genetic loci or variants for childhood intelligence have been reported. Here, we report the first genome-wide association study (GWAS) on childhood intelligence (age range 6-18 years) from 17,989 individuals in six discovery and three replication samples. Although no individual single-nucleotide polymorphisms (SNPs) were detected with genome-wide significance, we show that the aggregate effects of common SNPs explain 22-46% of phenotypic variation in childhood intelligence in the three largest cohorts (P=3.9 √? 10(-15), 0.014 and 0.028). FNBP1L, previously reported to be the most significantly associated gene for adult intelligence, was also significantly associated with childhood intelligence (P=0.003). Polygenic prediction analyses resulted in a significant correlation between predictor and outcome in all replication cohorts. The proportion of childhood intelligence explained by the predictor reached 1.2% (P=6 √? 10(-5)), 3.5% (P=10(-3)) and 0.5% (P=6 √? 10(-5)) in three independent validation cohorts. Given the sample sizes, these genetic prediction results are consistent with expectations if the genetic architecture of childhood intelligence is like that of body mass index or height. Our study provides molecular support for the heritability and polygenic nature of childhood intelligence. Larger sample sizes will be required to detect individual variants with genome-wide significance.
DATE PUBLISHED
2014 Feb
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2012/05/25
revised 2012/10/28
accepted 2012/11/12
aheadofprint 2013/01/29
entrez 2013/01/30 06:00
pubmed 2013/01/30 06:00
medline 2014/10/02 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Benyamin B Benyamin B B 1] The University of Queensland, Queensland Brain Institute, St Lucia, Queensland, Australia [2] Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
Pourcain B Pourcain Bst B Medical Research Council Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, UK.
Davis OS Davis O S OS King's College London, Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, London, UK.
Davies G Davies G G Department of Psychology, University of Edinburgh, Edinburgh, Scotland, UK.
Hansell NK Hansell N K NK Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
Brion MJ Brion M-J A MJ 1] Medical Research Council Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, UK [2] School of Women's and Infants' Health, The University of Western Australia, Perth, Western Australia, Australia.
Kirkpatrick RM Kirkpatrick R M RM Department of Psychology, University of Minnesota, St Paul, MN, USA.
Cents RA Cents R A M RA 1] The Generation R Study Group, Erasmus MC-University Medical Centre Rotterdam, Rotterdam, The Netherlands [2] Department of Child and Adolescent Psychiatry, Erasmus MC-University Medical Centre Rotterdam, Rotterdam, The Netherlands.
Franiń? S Franiń? S S Netherlands Twin Register, Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Miller MB Miller M B MB Department of Psychology, University of Minnesota, St Paul, MN, USA.
Haworth CM Haworth C M A CM King's College London, Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, London, UK.
Meaburn E Meaburn E E Department of Psychology, Birkbeck University of London, London, UK.
Price TS Price T S TS King's College London, Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, London, UK.
Evans DM Evans D M DM Medical Research Council Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, UK.
Timpson N Timpson N N Medical Research Council Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, UK.
Kemp J Kemp J J Medical Research Council Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, UK.
Ring S Ring S S Medical Research Council Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, UK.
McArdle W McArdle W W Medical Research Council Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, UK.
Medland SE Medland S E SE Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
Yang J Yang J J The University of Queensland Diamantina Institute, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
Harris SE Harris S E SE 1] Molecular Medicine Centre, Institute for Genetics and Molecular Medicine Centre, University of Edinburgh, Edinburgh, UK [2] Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
Liewald DC Liewald D C DC 1] Department of Psychology, University of Edinburgh, Edinburgh, Scotland, UK [2] Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
Scheet P Scheet P P Netherlands Twin Register, Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Xiao X Xiao X X Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Hudziak JJ Hudziak J J JJ Department of Psychiatry, College of Medicine, University of Vermont, Burlington, VT, USA.
de Geus EJ de Geus E J C EJ Netherlands Twin Register, Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Wellcome Trust Case Control Consortium 2 (WTCCC2)
Jaddoe VW Jaddoe V W V VW 1] The Generation R Study Group, Erasmus MC-University Medical Centre Rotterdam, Rotterdam, The Netherlands [2] Department of Epidemiology, Erasmus MC-University Medical Centre Rotterdam, Rotterdam, The Netherlands [3] Department of Pediatrics, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands.
Starr JM Starr J M JM 1] Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK [2] Alzheimer Scotland Dementia Research Centre, Department of Psychology, University of Edinburgh, Edinburgh, Scotland, UK.
Verhulst FC Verhulst F C FC Department of Child and Adolescent Psychiatry, Erasmus MC-University Medical Centre Rotterdam, Rotterdam, The Netherlands.
Pennell C Pennell C C School of Women's and Infants' Health, The University of Western Australia, Perth, Western Australia, Australia.
Tiemeier H Tiemeier H H 1] Department of Child and Adolescent Psychiatry, Erasmus MC-University Medical Centre Rotterdam, Rotterdam, The Netherlands [2] Department of Epidemiology, Erasmus MC-University Medical Centre Rotterdam, Rotterdam, The Netherlands [3] Department of Psychiatry, Erasmus MC-University Medical Centre Rotterdam, Rotterdam, The Netherlands.
Iacono WG Iacono W G WG Department of Psychology, University of Minnesota, St Paul, MN, USA.
Palmer LJ Palmer L J LJ 1] Genetic Epidemiology and Biostatistics Platform, Ontario Institute for Cancer Research, University of Toronto, Toronto, Ontario, Canada [2] Samuel Lunenfeld Research Institute, University of Toronto, Toronto, Ontario, Canada.
Montgomery GW Montgomery G W GW Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
Martin NG Martin N G NG Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
Boomsma DI Boomsma D I DI Netherlands Twin Register, Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Posthuma D Posthuma D D 1] Department of Child and Adolescent Psychiatry, Erasmus MC-University Medical Centre Rotterdam, Rotterdam, The Netherlands [2] Department of Functional Genomics, Center for Neurogenomics and Cognitive Research (CNCR), Neuroscience Campus Amsterdam (NCA), VU University Amsterdam and VU Medical Centre, Amsterdam, The Netherlands [3] Department of Clinical Genetics, Section Medical Genomics, VU Medical Centre, Amsterdam, The Netherlands.
McGue M McGue M M 1] Department of Psychology, University of Minnesota, St Paul, MN, USA [2] Department of Epidemiology, University of Southern Denmark, Odense, Denmark.
Wright MJ Wright M J MJ Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
Davey Smith G Davey Smith G G Medical Research Council Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, UK.
Deary IJ Deary I J IJ 1] Department of Psychology, University of Edinburgh, Edinburgh, Scotland, UK [2] Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
Plomin R Plomin R R King's College London, Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, London, UK.
Visscher PM Visscher P M PM 1] The University of Queensland, Queensland Brain Institute, St Lucia, Queensland, Australia [2] Queensland Institute of Medical Research, Brisbane, Queensland, Australia [3] The University of Queensland Diamantina Institute, Princess Alexandra Hospital, Brisbane, Queensland, Australia [4] Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
INVESTIGATORS
JOURNAL
VOLUME: 19
ISSUE: 2
TITLE: Molecular psychiatry
ISOABBREVIATION: Mol. Psychiatry
YEAR: 2014
MONTH: Feb
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1476-5578
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Mol Psychiatry
COUNTRY: England
ISSNLINKING: 1359-4184
NLMUNIQUEID: 9607835
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
092731 Wellcome Trust United Kingdom
BB/F019394/1 Biotechnology and Biological Sciences Research Council United Kingdom
CA55075 NCI NIH HHS United States
CA87969 NCI NIH HHS United States
DK58845 NIDDK NIH HHS United States
G0500079 Medical Research Council United Kingdom
G0700704 Medical Research Council United Kingdom
G9815508 Medical Research Council United Kingdom
R01 AA009367 NIAAA NIH HHS United States
R01 AA011886 NIAAA NIH HHS United States
R01 DA005147 NIDA NIH HHS United States
R01 DA013240 NIDA NIH HHS United States
R01 HD050735 NICHD NIH HHS United States
R01 MH066140 NIMH NIH HHS United States
R01HL086694 NHLBI NIH HHS United States
R01HL087641 NHLBI NIH HHS United States
R01HL59367 NHLBI NIH HHS United States
R37 DA005147 NIDA NIH HHS United States
U01 DA024417 NIDA NIH HHS United States
U01 HG004446 NHGRI NIH HHS United States
U01HG004399 NHGRI NIH HHS United States
U01HG004402 NHGRI NIH HHS United States
U01HG004424 NHGRI NIH HHS United States
UL1RR025005 NCRR NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adolescent
Carrier Proteins genetics
Child genetics
Cohort Studies genetics
European Continental Ancestry Group genetics
Female genetics
Genome-Wide Association Study genetics
Genotyping Techniques genetics
Humans genetics
Intelligence genetics
Intelligence Tests genetics
Male genetics
Multifactorial Inheritance genetics
Phenotype genetics
Polymorphism, Single Nucleotide genetics
Quantitative Trait, Heritable genetics
Software genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Carrier Proteins
0 FNBP1L protein, human
OTHER ID's
OTHERID SOURCE
NIHMS539571 NLM
PMC3935975 NLM