Genome-wide association meta- A nalysis 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- A nalysis 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. MagnussonMatt 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

Research output: Contribution to journal › Article › peer-review

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- A nalysis 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 (r_g = 0.89, LD score regression P = 5.4 × 10^-29). These findings provide new insight into the genetic architecture of intelligence.

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

ASJC Scopus subject areas

Genetics

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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- A nalysis 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

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- A nalysis 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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title = "Genome-wide association meta- A nalysis of 78,308 individuals identifies new loci and genes influencing human intelligence",

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- A nalysis 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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AU - Sniekers, Suzanne

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

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