Childhood intelligence is heritable, highly polygenic and associated with FNBP1L

被引：177

作者：

Benyamin, B. ^{[1
,2
]}

St Pourcain, B. ^{[3
]}

Davis, O. S. ^{[4
]}

Davies, G. ^{[5
]}

Hansell, N. K. ^{[2
]}

Brion, M-J A. ^{[3
]}

Kirkpatrick, R. M. ^{[7
]}

Cents, R. A. M. ^{[8
,9
]}

Franic, S. ^{[10
]}

Miller, M. B. ^{[7
]}

Haworth, C. M. A. ^{[4
]}

Meaburn, E. ^{[11
]}

Price, T. S. ^{[4
]}

Evans, D. M. ^{[3
]}

Timpson, N. ^{[3
]}

Kemp, J. ^{[3
]}

Ring, S. ^{[3
]}

McArdle, W. ^{[3
]}

Medland, S. E. ^{[2
]}

Yang, J. ^{[12
]}

Harris, S. E. ^{[13
,14
,15
]}

Liewald, D. C. ^{[5
,15
]}

Scheet, P. ^{[10
]}

Xiao, X. ^{[16
]}

Hudziak, J. J. ^{[17
]}

de Geus, E. J. C. ^{[10
]}

Jaddoe, V. W. V. ^{[8
,18
,19
]}

Starr, J. M. ^{[15
,20
]}

Verhulst, F. C. ^{[9
]}

Pennell, C. ^{[6
]}

Tiemeier, H. ^{[9
,18
,21
]}

Iacono, W. G. ^{[7
]}

Palmer, L. J. ^{[22
,23
]}

Montgomery, G. W. ^{[2
]}

Martin, N. G. ^{[2
]}

Boomsma, D. I. ^{[10
]}

Posthuma, D. ^{[9
,24
,25
,26
]}

McGue, M. ^{[7
,27
]}

Wright, M. J. ^{[2
]}

Smith, G. Davey ^{[3
]}

Deary, I. J. ^{[5
,15
]}

Plomin, R. ^{[4
]}

Visscher, P. M. ^{[1
,2
,12
,15
,18
]}

机构：

[1] Univ Queensland, Queensland Brain Inst, St Lucia, Qld 4072, Australia

[2] Queensland Inst Med Res, Brisbane, Qld 4006, Australia

[3] Univ Bristol, MRC, Ctr Causal Anal Translat Epidemiol, Bristol, Avon, England

[4] Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr, London WC2R 2LS, England

[5] Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland

[6] Univ Western Australia, Sch Womens & Infants Hlth, Perth, WA 6009, Australia

[7] Univ Minnesota, Dept Psychol, St Paul, MN 55108 USA

[8] Erasmus MC Univ, Med Ctr Rotterdam, Generat R Study Grp, Rotterdam, Netherlands

[9] Erasmus MC Univ, Med Ctr Rotterdam, Dept Child & Adolescent Psychiat, Rotterdam, Netherlands

[10] Vrije Univ Amsterdam, Dept Biol Psychol, Netherlands Twin Register, Amsterdam, Netherlands

[11] Birkbeck Univ London, Dept Psychol, London, England

[12] Univ Queensland, Princess Alexandra Hosp, Diamantina Inst, Brisbane, Qld, Australia

[13] Univ Edinburgh, Inst Genet, Mol Med Ctr, Edinburgh, Midlothian, Scotland

[14] Univ Edinburgh, Mol Med Ctr, Edinburgh, Midlothian, Scotland

[15] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland

[16] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA

[17] Univ Vermont, Coll Med, Dept Psychiat, Burlington, VT 05401 USA

[18] Erasmus MC Univ, Med Ctr Rotterdam, Dept Epidemiol, Rotterdam, Netherlands

[19] Erasmus MC, Dept Pediat, Rotterdam, Netherlands

[20] Univ Edinburgh, Dept Psychol, Alzheimer Scotland Dementia Res Ctr, Edinburgh, Midlothian, Scotland

[21] Erasmus MC Univ, Med Ctr Rotterdam, Dept Psychiat, Rotterdam, Netherlands

[22] Univ Toronto, Ontario Inst Canc Res, Genet Epidemiol & Biostat Platform, Toronto, ON, Canada

[23] Univ Toronto, Samuel Lunenfeld Res Inst, Toronto, ON, Canada

[24] Vrije Univ Amsterdam, NCA, CNCR, Dept Funct Genom, Amsterdam, Netherlands

[25] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands

[26] Vrije Univ Amsterdam Med Ctr, Sect Med Genom, Dept Clin Genet, Amsterdam, Netherlands

[27] Univ Southern Denmark, Dept Epidemiol, Odense, Denmark

来源：

MOLECULAR PSYCHIATRY | 2014年 / 19卷 / 02期

基金：

美国国家卫生研究院; 英国医学研究理事会; 英国生物技术与生命科学研究理事会;

关键词：

intelligence; IQ; cognitive; association; FNBP1L; polygenic; GENOME-WIDE ASSOCIATION; COMMON SNPS EXPLAIN; LARGE PROPORTION; HUMAN HEIGHT; ABILITY; LOCI; INDIVIDUALS; IMPUTATION; GENOTYPES; COMPLEX;

D O I：

10.1038/mp.2012.184

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 x 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 x 10(-5)), 3.5% (P = 10(-3)) and 0.5% (P = 6 x 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.

引用

页码：253 / 258

页数：6

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