Childhood intelligence is heritable, highly polygenic and associated with FNBP1L.
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.
1] The University of Queensland, Queensland Brain Institute, St Lucia, Queensland, Australia [2] Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
B
B
Benyamin
Medical Research Council Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, UK.
Bst
B
Pourcain
King's College London, Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, London, UK.
O S
OS
Davis
Department of Psychology, University of Edinburgh, Edinburgh, Scotland, UK.
G
G
Davies
Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
N K
NK
Hansell
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.
M-J A
MJ
Brion
Department of Psychology, University of Minnesota, St Paul, MN, USA.
R M
RM
Kirkpatrick
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.
R A M
RA
Cents
Netherlands Twin Register, Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
S
S
Franić
Department of Psychology, University of Minnesota, St Paul, MN, USA.
M B
MB
Miller
King's College London, Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, London, UK.
C M A
CM
Haworth
Department of Psychology, Birkbeck University of London, London, UK.
E
E
Meaburn
King's College London, Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, London, UK.
T S
TS
Price
Medical Research Council Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, UK.
D M
DM
Evans
Medical Research Council Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, UK.
N
N
Timpson
Medical Research Council Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, UK.
J
J
Kemp
Medical Research Council Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, UK.
S
S
Ring
Medical Research Council Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, UK.
W
W
McArdle
Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
S E
SE
Medland
The University of Queensland Diamantina Institute, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
J
J
Yang
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.
S E
SE
Harris
1] Department of Psychology, University of Edinburgh, Edinburgh, Scotland, UK [2] Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
D C
DC
Liewald
Netherlands Twin Register, Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
P
P
Scheet
Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
X
X
Xiao
Department of Psychiatry, College of Medicine, University of Vermont, Burlington, VT, USA.
J J
JJ
Hudziak
Netherlands Twin Register, Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
E J C
EJ
de Geus
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.
V W V
VW
Jaddoe
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.
J M
JM
Starr
Department of Child and Adolescent Psychiatry, Erasmus MC-University Medical Centre Rotterdam, Rotterdam, The Netherlands.
F C
FC
Verhulst
School of Women's and Infants' Health, The University of Western Australia, Perth, Western Australia, Australia.
C
C
Pennell
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.
H
H
Tiemeier
Department of Psychology, University of Minnesota, St Paul, MN, USA.
W G
WG
Iacono
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.
L J
LJ
Palmer
Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
G W
GW
Montgomery
Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
N G
NG
Martin
Netherlands Twin Register, Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
D I
DI
Boomsma
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.
D
D
Posthuma
1] Department of Psychology, University of Minnesota, St Paul, MN, USA [2] Department of Epidemiology, University of Southern Denmark, Odense, Denmark.
M
M
McGue
Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
M J
MJ
Wright
Medical Research Council Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, UK.
G
G
Davey Smith
1] Department of Psychology, University of Edinburgh, Edinburgh, Scotland, UK [2] Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
I J
IJ
Deary
King's College London, Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, London, UK.
R
R
Plomin
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.
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Visscher
D000293:Adolescent; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D015331:Cohort Studies; D005260:Female; D055106:Genome-Wide Association Study; D060005:Genotyping Techniques; D006801:Humans; D007360:Intelligence / Q000235:genetics*; D007361:Intelligence Tests; D008297:Male; D020412:Multifactorial Inheritance; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D019655:Quantitative Trait, Heritable; D012984:Software; D044465:White People / Q000235:genetics
D002352:Carrier Proteins; C482527:FNBP1L protein, human