|
|
| PMID |
|
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| 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 Ã? 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 Ã? 10(-5)), 3.5% (P=10(-3)) and 0.5% (P=6 Ã? 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. |
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| DATE PUBLISHED |
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| 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. |
| FraniÄ? S |
|
FraniÄ? |
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 |
|
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| 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 |
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| REFTYPE |
REFSOURCE |
REFPMID |
NOTE |
| Cites |
Cell. 2004 Jul 23;118(2):203-16 |
15260990 |
|
| Cites |
Nat Genet. 2007 Jul;39(7):906-13 |
17572673 |
|
| Cites |
Am J Hum Genet. 2007 Sep;81(3):559-75 |
17701901 |
|
| Cites |
Genes Brain Behav. 2008 Jun;7(4):435-46 |
18067574 |
|
| Cites |
Am J Hum Genet. 2009 Feb;84(2):210-23 |
19200528 |
|
| Cites |
Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9362-7 |
19474294 |
|
| Cites |
Hum Genet. 2009 Jul;126(1):215-32 |
19294424 |
|
| Cites |
Hum Mol Genet. 2009 Dec 1;18(23):4650-61 |
19734545 |
|
| Cites |
Am J Hum Genet. 2010 Feb 12;86(2):113-25 |
20060087 |
|
| Cites |
Nat Genet. 2010 Jul;42(7):565-9 |
20562875 |
|
| Cites |
Am J Hum Genet. 2010 Jul 9;87(1):139-45 |
20598278 |
|
| Cites |
Nature. 2010 Aug 5;466(7307):707-13 |
20686565 |
|
| Cites |
Nat Genet. 2009 Jun;41(6):677-87 |
19430479 |
|
| Cites |
Nature. 2010 Oct 14;467(7317):832-8 |
20881960 |
|
| Cites |
Mol Psychiatry. 2010 Nov;15(11):1112-20 |
19488046 |
|
| Cites |
Nat Genet. 2010 Nov;42(11):937-48 |
20935630 |
|
| Cites |
Genet Epidemiol. 2010 Dec;34(8):816-34 |
21058334 |
|
| Cites |
Behav Genet. 2010 Nov;40(6):759-67 |
20306291 |
|
| Cites |
Twin Res Hum Genet. 2010 Dec;13(6):517-24 |
21142928 |
|
| Cites |
Nat Genet. 2011 Jun;43(6):519-25 |
21552263 |
|
| Cites |
Eur J Hum Genet. 2011 Jul;19(7):807-12 |
21407268 |
|
| Cites |
Mol Psychiatry. 2011 Oct;16(10):996-1005 |
21826061 |
|
| Cites |
Annu Rev Psychol. 2012;63:453-82 |
21943169 |
|
| Cites |
Nature. 2011 Dec 8;480(7376):201-8 |
22139419 |
|
| Cites |
Psychol Sci. 2012;23(11):1314-23 |
23012269 |
|
| Cites |
Bioinformatics. 2010 Sep 1;26(17):2190-1 |
20616382 |
|
|
| 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 |
|
|
