Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

The genetic architecture of pediatric cognitive abilities in the Philadelphia Neurodevelopmental Cohort

Molecular Psychiatry volume 20, pages 454–458 (2015)Cite this article

Subjects

Abstract

The objective of this analysis was to examine the genetic architecture of diverse cognitive abilities in children and adolescents, including the magnitude of common genetic effects and patterns of shared and unique genetic influences. Subjects included 3689 members of the Philadelphia Neurodevelopmental Cohort, a general population sample comprising those aged 8–21 years who completed an extensive battery of cognitive tests. We used genome-wide complex trait analysis to estimate the SNP-based heritability of each domain, as well as the genetic correlation between all domains that showed significant genetic influence. Several of the individual domains suggested strong influence of common genetic variants (for example, reading ability, h2g=0.43, P=4e−06; emotion identification, h2g=0.36, P=1e−05; verbal memory, h2g=0.24, P=0.005). The genetic correlations highlighted trait domains that are candidates for joint interrogation in future genetic studies (for example, language reasoning and spatial reasoning, r(g)=0.72, P=0.007). These results can be used to structure future genetic and neuropsychiatric investigations of diverse cognitive abilities.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Wadsworth SJ, Corley RP, DeFries JC . Cognitive abilities in childhood and adolescence. In: Finkel D, Reynolds CA (eds). Behavior Genetics of Cognition Across the Lifespan. Springer: New York, NY, 2014, pp 3–40.

  2. Plomin R, DeFries JC, Knopik VS, Neiderhiser JM . General Cognitive Abilities. Behavioral Genetics, 6th edn. Worth: New York, NY, 2013.

    Google Scholar 

  3. Plomin R, DeFries JC, Knopik VS, Neiderhiser JM . Specific Cognitive Abilities. Behavioral Genetics, 6th edn. Worth: New York, NY, 2013.

    Google Scholar 

  4. Davies G, Tenesa A, Payton A, Yang J, Harris SE, Liewald D et al. Genome-wide association studies establish that human intelligence is highly heritable and polygenic. Mol Psychiatry 2011; 16: 996–1005.

    Article  CAS  Google Scholar 

  5. Benyamin B, Pourcain B, Davis OS, Davies G, Hansell NK, Brion MJ et al. Childhood intelligence is heritable, highly polygenic and associated with FNBP1L. Mol Psychiatry 2014; 19: 253–8.

    Article  CAS  Google Scholar 

  6. Deary IJ, Yang J, Davies G, Harris SE, Tenesa A, Liewald D et al. Genetic contributions to stability and change in intelligence from childhood to old age. Nature 2012; 482: 212–215.

    Article  CAS  Google Scholar 

  7. Plomin R, Haworth CM, Meaburn EL, Price TS, Davis OS . Common DNA markers can account for more than half of the genetic influence on cognitive abilities. Psychol Sci 2013; 24: 562–568.

    Article  Google Scholar 

  8. Yang J, Lee SH, Goddard ME, Visscher PM . GCTA: a tool for genome-wide complex trait analysis. Am J Hum Genet 2011; 88: 76–82.

    Article  CAS  Google Scholar 

  9. Greenwood TA, Braff DL, Light GA, Cadenhead KS, Calkins ME, Dobie DJ et al. Initial heritability analyses of endophenotypic measures for schizophrenia: the consortium on the genetics of schizophrenia. Arch Gen Psychiatry 2007; 64: 1242–1250.

    Article  Google Scholar 

  10. Stins JF, de Sonneville LM, Groot AS, Polderman TC, van Baal CG, Boomsma DI . Heritability of selective attention and working memory in preschoolers. Behav Genet 2005; 35: 407–416.

    Article  CAS  Google Scholar 

  11. Rietveld MJ, Hudziak JJ, Bartels M, van Beijsterveldt CE, Boomsma DI . Heritability of attention problems in children: longitudinal results from a study of twins, age 3 to 12. J Child Psychol Psychiatry 2004; 45: 577–588.

    Article  CAS  Google Scholar 

  12. Lundstrom S, Chang Z, Rastam M, Gillberg C, Larsson H, Anckarsater H et al. Autism spectrum disorders and autisticlike traits: similar etiology in the extreme end and the normal variation. Arch Gen Psychiatry 2012; 69: 46–52.

    Article  Google Scholar 

  13. Gur RE, Nimgaonkar VL, Almasy L, Calkins ME, Ragland JD, Pogue-Geile MF et al. Neurocognitive endophenotypes in a multiplex multigenerational family study of schizophrenia. Am J Psychiatry 2007; 164: 813–819.

    Article  Google Scholar 

  14. Sullivan PF, Daly MJ, O’Donovan M . Genetic architectures of psychiatric disorders: the emerging picture and its implications. Nat Rev Genet 2012; 13: 537–551.

    Article  CAS  Google Scholar 

  15. Trzaskowski M, Davis OS, DeFries JC, Yang J, Visscher PM, Plomin R . DNA evidence for strong genome-wide pleiotropy of cognitive and learning abilities. Behav Genet 2013; 43: 267–273.

    Article  Google Scholar 

  16. Kovas Y, Plomin R . Generalist genes: implications for the cognitive sciences. Trends Cogn Sci 2006; 10: 198–203.

    Article  Google Scholar 

  17. Trzaskowski M, Shakeshaft NG, Plomin R . Intelligence indexes generalist genes for cognitive abilities. Intelligence 2013; 41: 560–565.

    Article  Google Scholar 

  18. Lee SH, Ripke S, Neale BM, Faraone SV, Purcell SM, Perlis RH et al. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nat Genet 2013; 45: 984–994.

    Article  CAS  Google Scholar 

  19. Smoller JW, Craddock N, Kendler K, Lee PH, Neale BM, Nurnberger JI et al. Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet 2013; 381: 1371–1379.

    Article  CAS  Google Scholar 

  20. Gur RC, Richard J, Calkins ME, Chiavacci R, Hansen JA, Bilker WB et al. Age group and sex differences in performance on a computerized neurocognitive battery in children age 8–21. Neuropsychology 2012; 26: 251–265.

    Article  Google Scholar 

  21. Smith TD, Smith BL . Relationship between the Wide Range Achievement Test 3 and the Wechsler Individual Achievement Test. Psychol Rep 1998; 83 (3 Pt 1): 963–967.

    Article  CAS  Google Scholar 

  22. Yang J, Manolio TA, Pasquale LR, Boerwinkle E, Caporaso N, Cunningham JM et al. Genome partitioning of genetic variation for complex traits using common SNPs. Nat Genet 2011; 43: 519–525.

    Article  CAS  Google Scholar 

  23. Ripke S, Sanders AR, Kendler KS, Levinson DF, Sklar P, Holmans PA et al. Genome-wide association study identifies five new schizophrenia loci. Nat Genet 2011; 43: 969–976.

    Article  CAS  Google Scholar 

  24. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 2007; 81: 559–575.

    Article  CAS  Google Scholar 

  25. Inc SI . CSAS/STAT® 9.3 User's Guide. Care. SAS Institute Inc: Cary, NC, 2011.

    Google Scholar 

  26. Lee SH, DeCandia TR, Ripke S, Yang J, Sullivan PF, Goddard ME et al. Estimating the proportion of variation in susceptibility to schizophrenia captured by common SNPs. Nat Genet 2012; 44: 247–250.

    Article  CAS  Google Scholar 

  27. Neale BM, Kou Y, Liu L, Ma'ayan A, Samocha KE, Sabo A et al. Patterns and rates of exonic de novo mutations in autism spectrum disorders. Nature 2012; 485: 242–245.

    Article  CAS  Google Scholar 

  28. Gur RC, Richard J, Hughett P, Calkins ME, Macy L, Bilker WB et al. A cognitive neuroscience-based computerized battery for efficient measurement of individual differences: standardization and initial construct validation. J Neurosci Meth 2010; 187: 254–262.

    Article  Google Scholar 

  29. Haworth CM, Wright MJ, Luciano M, Martin NG, de Geus EJ, van Beijsterveldt CE et al. The heritability of general cognitive ability increases linearly from childhood to young adulthood. Mol Psychiatry 2010; 15: 1112–1120.

    Article  CAS  Google Scholar 

  30. Hoekstra RA, Barterls M, Boomsma DI . Longitudinal genetic study of verbal and nonverbal IQ from early childhood to young adulthood. Learn Indiv Differ 2007; 17: 97–114.

    Article  Google Scholar 

  31. Plomin R, Haworth CM, Davis OS . Common disorders are quantitative traits. Nat Rev Genet 2009; 10: 872–878.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We greatly appreciate the efforts of the participants and families involved in the Philadelphia Neurodevelopmental Cohort. The PNC was supported by NIH RC2 grants MH089983 and MH089924. EBR was funded by grant 1K01MH099286-01A1 from the National Institutes of Mental Health.

Author information

Author notes

  1. R Gur and H Hakonarson: Information about the Philadelphia Neurodevelopmental Cohort can be found at raquel@mail.med.upenn.edu and hakonarson@email.chop.edu.

  2. R Gur and H Hakonarson: These authors contributed equally to this work.

Authors and Affiliations

  1. Massachusetts General Hospital and Department of Medicine, Analytic and Translational Genetics Unit, Harvard Medical School, Boston, MA, USA

    E B Robinson, A Kirby, V Anttila, B M Neale & M J Daly

  2. Stanley Center for Psychiatric Research and Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA

    E B Robinson, A Kirby, V Anttila, B M Neale & M J Daly

  3. Department of Psychiatry, Perelman of School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    K Ruparel, R Gur & R Gur

  4. Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia

    J Yang

  5. Center for Human Genetic Research and Department of Psychiatry, Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, USA

    L McGrath

  6. Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland

    V Anttila

  7. Genetic Epidemiology Research Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA

    K Merikangas

  8. Office of Genomics Research Coordination, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA

    T Lehner

  9. Center for Applied Genomics, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    P M A Sleiman & H Hakonarson

Authors
  1. E B Robinson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A Kirby
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K Ruparel
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. L McGrath
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. V Anttila
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. B M Neale
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. K Merikangas
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. T Lehner
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. P M A Sleiman
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. M J Daly
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. R Gur
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. R Gur
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. H Hakonarson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to E B Robinson.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies the paper on the Molecular Psychiatry website

Supplementary information

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Robinson, E., Kirby, A., Ruparel, K. et al. The genetic architecture of pediatric cognitive abilities in the Philadelphia Neurodevelopmental Cohort. Mol Psychiatry 20, 454–458 (2015). https://doi.org/10.1038/mp.2014.65

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/mp.2014.65

Search

Advanced search

Quick links