Childhood intelligence is heritable, highly polygenic and associated with FNBP1L

doi:10.1038/mp.2012.184

Meta-Analysis

. 2014 Feb;19(2):253-8.

doi: 10.1038/mp.2012.184. Epub 2013 Jan 29.

Childhood intelligence is heritable, highly polygenic and associated with FNBP1L

B Benyamin¹, Bst Pourcain², O S Davis³, G Davies⁴, N K Hansell⁵, M-J A Brion⁶, R M Kirkpatrick⁷, R A M Cents⁸, S Franić⁹, M B Miller⁷, C M A Haworth³, E Meaburn¹⁰, T S Price³, D M Evans², N Timpson², J Kemp², S Ring², W McArdle², S E Medland⁵, J Yang¹¹, S E Harris¹², D C Liewald¹³, P Scheet⁹, X Xiao¹⁴, J J Hudziak¹⁵, E J C de Geus⁹; Wellcome Trust Case Control Consortium 2 (WTCCC2); V W V Jaddoe¹⁶, J M Starr¹⁷, F C Verhulst¹⁸, C Pennell¹⁹, H Tiemeier²⁰, W G Iacono⁷, L J Palmer²¹, G W Montgomery⁵, N G Martin⁵, D I Boomsma⁹, D Posthuma²², M McGue²³, M J Wright⁵, G Davey Smith², I J Deary¹³, R Plomin³, P M Visscher²⁴

Affiliations

¹ 1] The University of Queensland, Queensland Brain Institute, St Lucia, Queensland, Australia [2] Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
² Medical Research Council Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, UK.
³ King's College London, Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, London, UK.
⁴ Department of Psychology, University of Edinburgh, Edinburgh, Scotland, UK.
⁵ Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
⁶ 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.
⁷ Department of Psychology, University of Minnesota, St Paul, MN, USA.
⁸ 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.
⁹ Netherlands Twin Register, Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
¹⁰ Department of Psychology, Birkbeck University of London, London, UK.
¹¹ The University of Queensland Diamantina Institute, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
¹² 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.
¹³ 1] Department of Psychology, University of Edinburgh, Edinburgh, Scotland, UK [2] Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
¹⁴ Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
¹⁵ Department of Psychiatry, College of Medicine, University of Vermont, Burlington, VT, USA.
¹⁶ 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.
¹⁷ 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.
¹⁸ Department of Child and Adolescent Psychiatry, Erasmus MC-University Medical Centre Rotterdam, Rotterdam, The Netherlands.
¹⁹ School of Women's and Infants' Health, The University of Western Australia, Perth, Western Australia, Australia.
²⁰ 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.
²¹ 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.
²² 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.
²³ 1] Department of Psychology, University of Minnesota, St Paul, MN, USA [2] Department of Epidemiology, University of Southern Denmark, Odense, Denmark.
²⁴ 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.

PMID: 23358156
PMCID: PMC3935975
DOI: 10.1038/mp.2012.184

Meta-Analysis

Childhood intelligence is heritable, highly polygenic and associated with FNBP1L

B Benyamin et al. Mol Psychiatry. 2014 Feb.

. 2014 Feb;19(2):253-8.

doi: 10.1038/mp.2012.184. Epub 2013 Jan 29.

Authors

Affiliations

¹ 1] The University of Queensland, Queensland Brain Institute, St Lucia, Queensland, Australia [2] Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
² Medical Research Council Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Bristol, UK.
³ King's College London, Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, London, UK.
⁴ Department of Psychology, University of Edinburgh, Edinburgh, Scotland, UK.
⁵ Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
⁶ 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.
⁷ Department of Psychology, University of Minnesota, St Paul, MN, USA.
⁸ 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.
⁹ Netherlands Twin Register, Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
¹⁰ Department of Psychology, Birkbeck University of London, London, UK.
¹¹ The University of Queensland Diamantina Institute, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
¹² 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.
¹³ 1] Department of Psychology, University of Edinburgh, Edinburgh, Scotland, UK [2] Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
¹⁴ Department of Epidemiology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
¹⁵ Department of Psychiatry, College of Medicine, University of Vermont, Burlington, VT, USA.
¹⁶ 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.
¹⁷ 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.
¹⁸ Department of Child and Adolescent Psychiatry, Erasmus MC-University Medical Centre Rotterdam, Rotterdam, The Netherlands.
¹⁹ School of Women's and Infants' Health, The University of Western Australia, Perth, Western Australia, Australia.
²⁰ 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.
²¹ 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.
²² 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.
²³ 1] Department of Psychology, University of Minnesota, St Paul, MN, USA [2] Department of Epidemiology, University of Southern Denmark, Odense, Denmark.
²⁴ 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.

PMID: 23358156
PMCID: PMC3935975
DOI: 10.1038/mp.2012.184

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.

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Conflict of interest statement

Conflict of Interest: The authors declare no conflict of interest.

Figures

**Figure 1**
Manhattan and Q–Q plots of P-values of the association between single-nucleotide polymorphisms (SNPs) and Intelligence Quotient (IQ) in the discovery samples.

**Figure 2**
The proportion of the phenotypic variance in childhood intelligence explained by multi-single-nucleotide polymorphisms (SNPs) predictors (R²) in three replication samples. Each bar represents R² for a given set of multi-SNPs predictors at a given P-value threshold.

See this image and copyright information in PMC

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References

1. Deary IJ. Intelligence. Annu Rev Psychol. 2012;63:453–482. - PubMed
1. Deary IJ, Johnson W, Houlihan LM. Genetic foundations of human intelligence. Hum Genet. 2009;126:215–232. - PubMed
1. Chabris CF. Most reported genetic associations with general intelligence are probably false positives. Psychol Sci. 2011;23:1314–1323. - PMC - PubMed
1. Hindorff LA, Sethupathy P, Junkins HA, Ramos EM, Mehta JP, Collins FS, et al. Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc Natl Acad Sci USA. 2009;106:9362–9367. - PMC - PubMed
1. Need AC, Attix DK, McEvoy JM, Cirulli ET, Linney KL, Hunt P, et al. A genome-wide study of common SNPs and CNVs in cognitive performance in the CANTAB. Hum Mol Genet. 2009;18:4650–4661. - PMC - PubMed

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[1] Deary IJ. Intelligence. Annu Rev Psychol. 2012;63:453–482. - PubMed

[2] Deary IJ. Intelligence. Annu Rev Psychol. 2012;63:453–482. - PubMed

[3] Deary IJ, Johnson W, Houlihan LM. Genetic foundations of human intelligence. Hum Genet. 2009;126:215–232. - PubMed

[4] Deary IJ, Johnson W, Houlihan LM. Genetic foundations of human intelligence. Hum Genet. 2009;126:215–232. - PubMed

[5] Chabris CF. Most reported genetic associations with general intelligence are probably false positives. Psychol Sci. 2011;23:1314–1323. - PMC - PubMed

[6] Chabris CF. Most reported genetic associations with general intelligence are probably false positives. Psychol Sci. 2011;23:1314–1323. - PMC - PubMed

[7] Hindorff LA, Sethupathy P, Junkins HA, Ramos EM, Mehta JP, Collins FS, et al. Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc Natl Acad Sci USA. 2009;106:9362–9367. - PMC - PubMed

[8] Hindorff LA, Sethupathy P, Junkins HA, Ramos EM, Mehta JP, Collins FS, et al. Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc Natl Acad Sci USA. 2009;106:9362–9367. - PMC - PubMed

[9] Need AC, Attix DK, McEvoy JM, Cirulli ET, Linney KL, Hunt P, et al. A genome-wide study of common SNPs and CNVs in cognitive performance in the CANTAB. Hum Mol Genet. 2009;18:4650–4661. - PMC - PubMed

[10] Need AC, Attix DK, McEvoy JM, Cirulli ET, Linney KL, Hunt P, et al. A genome-wide study of common SNPs and CNVs in cognitive performance in the CANTAB. Hum Mol Genet. 2009;18:4650–4661. - PMC - PubMed

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Childhood intelligence is heritable, highly polygenic and associated with FNBP1L

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Childhood intelligence is heritable, highly polygenic and associated with FNBP1L

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