Genome-wide association meta-analysis of 78,308 individuals identifies new loci and genes influencing human intelligence

Suzanne Sniekers; Sven Stringer; Kyoko Watanabe; Philip R Jansen; Jonathan R I Coleman; Eva Krapohl; Erdogan Taskesen; Anke R Hammerschlag; Aysu Okbay; Delilah Zabaneh; Najaf Amin; Gerome Breen; David Cesarini; Christopher F Chabris; William G Iacono; M Arfan Ikram; Magnus Johannesson; Philipp Koellinger; James J Lee; Patrik K E Magnusson; Matt McGue; Mike B Miller; William E R Ollier; Antony Payton; Neil Pendleton; Robert Plomin; Cornelius A Rietveld; Henning Tiemeier; Cornelia M van Duijn; Danielle Posthuma

doi:10.1038/ng.3869

Genome-wide association meta-analysis of 78,308 individuals identifies new loci and genes influencing human intelligence

Suzanne Sniekers
, Sven Stringer
, Kyoko Watanabe
, Philip R Jansen
, Jonathan R I Coleman
, Eva Krapohl
, Erdogan Taskesen
, Anke R Hammerschlag
, Aysu Okbay
, Delilah Zabaneh
, Najaf Amin
, Gerome Breen
, David Cesarini
, Christopher F Chabris
, William G Iacono
, M Arfan Ikram
, Magnus Johannesson
, Philipp Koellinger
, James J Lee
, Patrik K E Magnusson

Matt McGue, Mike B Miller, William E R Ollier, Antony Payton, Neil Pendleton, Robert Plomin, Cornelius A Rietveld, Henning Tiemeier, Cornelia M van Duijn, Danielle Posthuma

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Abstract

Intelligence is associated with important economic and health-related life outcomes. Despite intelligence having substantial heritability (0.54) and a confirmed polygenic nature, initial genetic studies were mostly underpowered. Here we report a meta-analysis for intelligence of 78,308 individuals. We identify 336 associated SNPs (METAL P < 5 × 10-8) in 18 genomic loci, of which 15 are new. Around half of the SNPs are located inside a gene, implicating 22 genes, of which 11 are new findings. Gene-based analyses identified an additional 30 genes (MAGMA P < 2.73 × 10-6), of which all but one had not been implicated previously. We show that the identified genes are predominantly expressed in brain tissue, and pathway analysis indicates the involvement of genes regulating cell development (MAGMA competitive P = 3.5 × 10-6). Despite the well-known difference in twin-based heritability for intelligence in childhood (0.45) and adulthood (0.80), we show substantial genetic correlation (rg = 0.89, LD score regression P = 5.4 × 10-29). These findings provide new insight into the genetic architecture of intelligence.

Original language	English
Pages (from-to)	1107-1112
Number of pages	6
Journal	Nature Genetics
Volume	49
Issue number	7
Early online date	22 May 2017
DOIs	https://doi.org/10.1038/ng.3869
Publication status	Published - 1 Jul 2017

Funding

Funders	Funder number
Medical Research Council	G0901461, G0600237, G0900753, G0500079, G0901245, G19/2, MR/M021475/1, MR/K002279/1, MC_qA137853, G0100594
National Institute on Drug Abuse	R01DA036216, F31DA029377, R01DA005147, R01DA013240, R01DA024417
National Institute of Diabetes and Digestive and Kidney Diseases	U01DK066134
National Institute on Alcohol Abuse and Alcoholism	R01AA011886, R37AA009367
National Institute on Aging	T32AG000186
Biotechnology and Biological Sciences Research Council	BB/F022441/1
Horizon 2020 Framework Programme	647648
National Institute of Mental Health	T32MH016880, R01MH066140
???publication-publication-funding-organisation-not-added???	480-05-003

Keywords

Adolescent
Adult
Aged
Brain
Child
Child, Preschool
European Continental Ancestry Group
Female
Genome-Wide Association Study
Humans
Infant
Intelligence
Journal Article
Linkage Disequilibrium
Male
Meta-Analysis
Middle Aged
Nerve Tissue Proteins
Polymorphism, Single Nucleotide
Young Adult

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10.1038/ng.3869

ng.3869_Genome-wide association meta-analysis of 78,308 individuals identifies new loci and genes influencing human intelligenceFinal published version, 6.76 MBLicence: Article 25fa Dutch Copyright Act

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Sniekers, S., Stringer, S., Watanabe, K., Jansen, P. R., Coleman, J. R. I., Krapohl, E., Taskesen, E., Hammerschlag, A. R., Okbay, A., Zabaneh, D., Amin, N., Breen, G., Cesarini, D., Chabris, C. F., Iacono, W. G., Ikram, M. A., Johannesson, M., Koellinger, P., Lee, J. J., ... Posthuma, D. (2017). Genome-wide association meta-analysis of 78,308 individuals identifies new loci and genes influencing human intelligence. Nature Genetics, 49(7), 1107-1112. https://doi.org/10.1038/ng.3869

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abstract = "Intelligence is associated with important economic and health-related life outcomes. Despite intelligence having substantial heritability (0.54) and a confirmed polygenic nature, initial genetic studies were mostly underpowered. Here we report a meta-analysis for intelligence of 78,308 individuals. We identify 336 associated SNPs (METAL P < 5 × 10-8) in 18 genomic loci, of which 15 are new. Around half of the SNPs are located inside a gene, implicating 22 genes, of which 11 are new findings. Gene-based analyses identified an additional 30 genes (MAGMA P < 2.73 × 10-6), of which all but one had not been implicated previously. We show that the identified genes are predominantly expressed in brain tissue, and pathway analysis indicates the involvement of genes regulating cell development (MAGMA competitive P = 3.5 × 10-6). Despite the well-known difference in twin-based heritability for intelligence in childhood (0.45) and adulthood (0.80), we show substantial genetic correlation (rg = 0.89, LD score regression P = 5.4 × 10-29). These findings provide new insight into the genetic architecture of intelligence.",

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Sniekers, S, Stringer, S, Watanabe, K, Jansen, PR, Coleman, JRI, Krapohl, E, Taskesen, E, Hammerschlag, AR, Okbay, A, Zabaneh, D, Amin, N, Breen, G, Cesarini, D, Chabris, CF, Iacono, WG, Ikram, MA, Johannesson, M, Koellinger, P, Lee, JJ, Magnusson, PKE, McGue, M, Miller, MB, Ollier, WER, Payton, A, Pendleton, N, Plomin, R, Rietveld, CA, Tiemeier, H, van Duijn, CM & Posthuma, D 2017, 'Genome-wide association meta-analysis of 78,308 individuals identifies new loci and genes influencing human intelligence', Nature Genetics, vol. 49, no. 7, pp. 1107-1112. https://doi.org/10.1038/ng.3869

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T1 - Genome-wide association meta-analysis of 78,308 individuals identifies new loci and genes influencing human intelligence

AU - Sniekers, Suzanne

AU - Stringer, Sven

AU - Watanabe, Kyoko

AU - Jansen, Philip R

AU - Coleman, Jonathan R I

AU - Krapohl, Eva

AU - Taskesen, Erdogan

AU - Hammerschlag, Anke R

AU - Okbay, Aysu

AU - Zabaneh, Delilah

AU - Amin, Najaf

AU - Breen, Gerome

AU - Cesarini, David

AU - Chabris, Christopher F

AU - Iacono, William G

AU - Ikram, M Arfan

AU - Johannesson, Magnus

AU - Koellinger, Philipp

AU - Lee, James J

AU - Magnusson, Patrik K E

AU - McGue, Matt

AU - Miller, Mike B

AU - Ollier, William E R

AU - Payton, Antony

AU - Pendleton, Neil

AU - Plomin, Robert

AU - Rietveld, Cornelius A

AU - Tiemeier, Henning

AU - van Duijn, Cornelia M

AU - Posthuma, Danielle

PY - 2017/7/1

Y1 - 2017/7/1

N2 - Intelligence is associated with important economic and health-related life outcomes. Despite intelligence having substantial heritability (0.54) and a confirmed polygenic nature, initial genetic studies were mostly underpowered. Here we report a meta-analysis for intelligence of 78,308 individuals. We identify 336 associated SNPs (METAL P < 5 × 10-8) in 18 genomic loci, of which 15 are new. Around half of the SNPs are located inside a gene, implicating 22 genes, of which 11 are new findings. Gene-based analyses identified an additional 30 genes (MAGMA P < 2.73 × 10-6), of which all but one had not been implicated previously. We show that the identified genes are predominantly expressed in brain tissue, and pathway analysis indicates the involvement of genes regulating cell development (MAGMA competitive P = 3.5 × 10-6). Despite the well-known difference in twin-based heritability for intelligence in childhood (0.45) and adulthood (0.80), we show substantial genetic correlation (rg = 0.89, LD score regression P = 5.4 × 10-29). These findings provide new insight into the genetic architecture of intelligence.

AB - Intelligence is associated with important economic and health-related life outcomes. Despite intelligence having substantial heritability (0.54) and a confirmed polygenic nature, initial genetic studies were mostly underpowered. Here we report a meta-analysis for intelligence of 78,308 individuals. We identify 336 associated SNPs (METAL P < 5 × 10-8) in 18 genomic loci, of which 15 are new. Around half of the SNPs are located inside a gene, implicating 22 genes, of which 11 are new findings. Gene-based analyses identified an additional 30 genes (MAGMA P < 2.73 × 10-6), of which all but one had not been implicated previously. We show that the identified genes are predominantly expressed in brain tissue, and pathway analysis indicates the involvement of genes regulating cell development (MAGMA competitive P = 3.5 × 10-6). Despite the well-known difference in twin-based heritability for intelligence in childhood (0.45) and adulthood (0.80), we show substantial genetic correlation (rg = 0.89, LD score regression P = 5.4 × 10-29). These findings provide new insight into the genetic architecture of intelligence.

KW - Adolescent

KW - Adult

KW - Aged

KW - Brain

KW - Child

KW - Child, Preschool

KW - European Continental Ancestry Group

KW - Female

KW - Genome-Wide Association Study

KW - Humans

KW - Infant

KW - Intelligence

KW - Journal Article

KW - Linkage Disequilibrium

KW - Male

KW - Meta-Analysis

KW - Middle Aged

KW - Nerve Tissue Proteins

KW - Polymorphism, Single Nucleotide

KW - Young Adult

UR - https://www.scopus.com/pages/publications/85020899420

UR - https://www.scopus.com/pages/publications/85020899420#tab=citedBy

U2 - 10.1038/ng.3869

DO - 10.1038/ng.3869

M3 - Article

C2 - 28530673

SN - 1061-4036

VL - 49

SP - 1107

EP - 1112

JO - Nature Genetics

JF - Nature Genetics

IS - 7

ER -

Genome-wide association meta-analysis of 78,308 individuals identifies new loci and genes influencing human intelligence

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Keywords

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