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A genome-wide association study for extremely high intelligence

Open access
Zabaneh, D, Krapohl, E, Gaspar, H A, Curtis, C, Lee, S H, Patel, H, Newhouse, S, Wu, H M +5 more·2018·Molecular Psychiatry
DOI 10.1038/mp.2017.121PMC PMC5987166
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Abstract

We used a case-control genome-wide association (GWA) design with cases consisting of 1238 individuals from the top 0.0003 (~170 mean IQ) of the population distribution of intelligence and 8172 unselected population-based controls. The single-nucleotide polymorphism heritability for the extreme IQ trait was 0.33 (0.02), which is the highest so far for a cognitive phenotype, and significant genome-wide genetic correlations of 0.78 were observed with educational attainment and 0.86 with population IQ. Three variants in locus ADAM12 achieved genome-wide significance, although they did not replicate with published GWA analyses of normal-range IQ or educational attainment. A genome-wide polygenic score constructed from the GWA results accounted for 1.6% of the variance of intelligence in the normal range in an unselected sample of 3414 individuals, which is comparable to the variance explained by GWA studies of intelligence with substantially larger sample sizes. The gene family plexins, members of which are mutated in several monogenic neurodevelopmental disorders, was significantly enriched for associations with high IQ. This study shows the utility of extreme trait selection for genetic study of intelligence and suggests that extremely high intelligence is continuous genetically with normal-range intelligence in the population.

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  • Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence.

    “Recent genome-wide metaanalyses have identified 24 genomic loci linked to variation in intelligence 3-7”

    From Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence (2018) · cites this paper as [7]

    The Results (Analysis of genome-wide SNPs; page unavailable) identify three significant SNPs at one ADAM12 locus, and the Introduction discusses earlier genome-wide studies of intelligence. Neither passage supports the specific claim that meta-analyses identified 24 loci. (LLM, conf=0.83)

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Authors
Zabaneh, D., Krapohl, E., Gaspar, H. A., Curtis, C., Lee, S. H., Patel, H., Newhouse, S., Wu, H. M., Simpson, M. A., Putallaz, M., Lubinski, D., Plomin, R., & Breen, G.
Affiliations
  • King's College London (GB)
  • Guy's Hospital (GB)
  • Duke University (US)
  • Vanderbilt University (US)
Corresponding author
Breen, G
ORCID
Venue
Molecular Psychiatry
Publisher
Springer Science and Business Media LLC
Published
2017-07-04
Volume
23
Issue
5
Pages
1226-1232
ISSN
  • 1359-4184 (ISSN-L)
  • 1476-5578
DOI
10.1038/mp.2017.121
PMC
PMC5987166
OpenAlex
W2728946616
Cited by
71
References
8
Citations by year
2026: 1 · 2025: 6 · 2024: 2 · 2023: 6 · 2022: 9 · 2021: 11 · 2020: 19 · 2019: 7 · 2018: 6 · 2017: 3 · 2015: 1
FWCI
6.35
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Psychiatry (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • UniSA Research Outputs Repository (University of South Australia) (acceptedVersion, cc-by-nc-sa)
  • Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion, cc-by-nc-sa)
  • Research Portal (King's College London) (submittedVersion, cc-by-nc-sa)
Funders
  • John Templeton Foundation
  • South London and Maudsley NHS Foundation Trust
  • Maudsley Charity
  • National Institute for Health and Care Research
  • King's College London
  • European Commission (295366, 602768)
  • National Institutes of Health (G0901245, 602768, MR/M021475/1, AG046938)
  • Institute of Psychiatry, Psychology and Neuroscience, King’s College London
  • Medical Research Council (G0901245, MR/M021475, MR/M021475/1, 602768, 295366, AG046938, MR/M021475/1 and previously G0901245)
  • National Institute on Aging (R01AG046938)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD044454)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Cognitive Abilities and Testing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
Keywords
genetic correlation, educational attainment, ADAM12, polygenic risk score, plexins
MeSH terms
ADAM12 Protein, Adolescent, Adult, Female, Humans, Intelligence, Longitudinal Studies, Male, Phenotype, Case-Control Studies, Quantitative Trait, Heritable, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Genome-Wide Association Study

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