• An Erratum to this article was published on 27 September 2017

Abstract

Intelligence is associated with important economic and health-related life outcomes1. Despite intelligence having substantial heritability2 (0.54) and a confirmed polygenic nature, initial genetic studies were mostly underpowered3,4,5. 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 heritability2 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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Change history

  • Corrected online 31 May 2017

    In the version of this article initially published online, heritability was misspelled in the penultimate sentence of the abstract. The error has been corrected in the print, PDF and HTML versions of this article.

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Acknowledgements

This work was funded by the Netherlands Organization for Scientific Research (NWO VICI 453-14-005). The analyses were carried out on the Genetic Cluster Computer, which is financed by the Netherlands Scientific Organization (NWO: 480-05-003), by VU University, Amsterdam, the Netherlands, and by the Dutch Brain Foundation and is hosted by the Dutch National Computing and Networking Services SurfSARA. This research has been conducted using the UK Biobank resource under application number 16406. We thank the participants and researchers who collected and contributed to the data.

Summary statistics have been made available for download from http://ctg.cncr.nl/software/summary_statistics.

Author information

Author notes

    • Christopher F Chabris

    Present address: Geisinger Health System, Danville, Pennsylvania, USA.

Affiliations

  1. Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University Amsterdam, Amsterdam, the Netherlands.

    • Suzanne Sniekers
    • , Sven Stringer
    • , Kyoko Watanabe
    • , Philip R Jansen
    • , Erdogan Taskesen
    • , Anke R Hammerschlag
    • , Aysu Okbay
    • , Philipp Koellinger
    •  & Danielle Posthuma
  2. Department of Child and Adolescent Psychiatry, Erasmus Medical Center, Rotterdam, the Netherlands.

    • Philip R Jansen
    •  & Henning Tiemeier
  3. MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

    • Jonathan R I Coleman
    • , Eva Krapohl
    • , Delilah Zabaneh
    • , Gerome Breen
    •  & Robert Plomin
  4. NIHR Biomedical Research Centre for Mental Health, South London and Maudsley NHS Trust, London, UK.

    • Jonathan R I Coleman
    •  & Gerome Breen
  5. Alzheimer Centrum, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, the Netherlands.

    • Erdogan Taskesen
  6. Erasmus University Rotterdam Institute for Behavior and Biology, Rotterdam, the Netherlands.

    • Aysu Okbay
    • , Philipp Koellinger
    •  & Cornelius A Rietveld
  7. Genetic Epidemiology Unit, Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.

    • Najaf Amin
    •  & Cornelia M van Duijn
  8. Center for Experimental Social Science, Department of Economics, New York University, New York, New York, USA.

    • David Cesarini
  9. Department of Psychology, Union College, Schenectady, New York, USA.

    • Christopher F Chabris
  10. Department of Psychology, University of Minnesota, Minneapolis, Minnesota, USA.

    • William G Iacono
    • , James J Lee
    • , Matt McGue
    •  & Mike B Miller
  11. Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.

    • M Arfan Ikram
    •  & Henning Tiemeier
  12. Department of Economics, Stockholm School of Economics, Stockholm, Sweden.

    • Magnus Johannesson
  13. Department of Psychology, Harvard University, Cambridge, Massachusetts, USA.

    • James J Lee
  14. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

    • Patrik K E Magnusson
  15. Centre for Epidemiology, Division of Population Health, Health Services Research and Primary Care, University of Manchester, Manchester, UK.

    • William E R Ollier
    •  & Antony Payton
  16. Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.

    • Neil Pendleton
  17. Department of Applied Economics, Erasmus School of Economics, Erasmus University Rotterdam, Rotterdam, the Netherlands.

    • Cornelius A Rietveld
  18. Department of Psychiatry, Erasmus Medical Center, Rotterdam, the Netherlands.

    • Henning Tiemeier
  19. Translational Epidemiology, Faculty Science, Leiden University, Leiden, the Netherlands.

    • Cornelia M van Duijn
  20. Department of Clinical Genetics, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, the Netherlands.

    • Danielle Posthuma

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Contributions

S. Sniekers performed the analyses. D.P. conceived the study. S. Stringer performed quality control on the UK Biobank data. K.W. and E.T. conducted in silico follow-up analyses. P.R.J., E.K. and J.R.I.C. conducted polygenic risk score analyses. P.K., C.A.R., D.Z., H.T., C.M.v.D., N.A., P.M., D.C., M.J., M.M., M.B.M., W.G.I., J.J.L., G.B., R.P., N.P., A.P., W.E.R.O., M.A.I. and C.F.C. contributed data. A.R.H. provided scripts for the pathway analyses. A.O. performed the educational attainment meta-analysis. S. Sniekers and D.P. wrote the manuscript. All authors discussed the results and commented on the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Danielle Posthuma.

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