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Biological annotation of genetic loci associated with intelligence in a meta-analysis of 87,740 individuals

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Coleman, Jonathan R. I., Bryois, Julien, Gaspar, Héléna A., Jansen, Philip R., Savage, Jeanne E., Skene, Nathan, Plomin, Robert, Muñoz-Manchado, Ana B. +6 more·2019·Molecular Psychiatry
DOI 10.1038/s41380-018-0040-6PMC PMC6330082

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Abstract

Variance in IQ is associated with a wide range of health outcomes, and 1% of the population are affected by intellectual disability. Despite a century of research, the fundamental neural underpinnings of intelligence remain unclear. We integrate results from genome-wide association studies (GWAS) of intelligence with brain tissue and single cell gene expression data to identify tissues and cell types associated with intelligence. GWAS data for IQ (N = 78,308) were meta-analyzed with a study comparing 1247 individuals with mean IQ ~170 to 8185 controls. Genes associated with intelligence implicate pyramidal neurons of the somatosensory cortex and CA1 region of the hippocampus, and midbrain embryonic GABAergic neurons. Tissue-specific analyses find the most significant enrichment for frontal cortex brain expressed genes. These results suggest specific neuronal cell types and genes may be involved in intelligence and provide new hypotheses for neuroscience experiments using model systems.

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Authors
Coleman, J. R. I., Bryois, J., Gaspar, H. A., Jansen, P. R., Savage, J. E., Skene, N., Plomin, R., Muñoz-Manchado, A. B., Linnarsson, S., Crawford, G., Hjerling-Leffler, J., Sullivan, P. F., Posthuma, D., & Breen, G.
Affiliations
  • King's College London (GB)
  • Karolinska Institutet (SE)
  • Erasmus MC (NL)
  • Vrije Universiteit Amsterdam (NL)
  • Duke University (US)
  • University of North Carolina at Chapel Hill (US)
Corresponding author
Breen, Gerome
ORCID
Venue
Molecular Psychiatry
Publisher
Springer Science and Business Media LLC
Published
2018-03-08
Volume
24
Issue
2
Pages
182-197
ISSN
  • 1359-4184 (ISSN-L)
  • 1476-5578
DOI
10.1038/s41380-018-0040-6
PMC
PMC6330082
OpenAlex
W2792859845
Cited by
66
References
9
Citations by year
2026: 2 · 2025: 7 · 2024: 8 · 2023: 6 · 2022: 10 · 2021: 8 · 2020: 14 · 2019: 7 · 2018: 3 · 2017: 1
FWCI
1.12
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Molecular Psychiatry (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Pure Amsterdam UMC (publishedVersion, other-oa)
  • EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • RODIN (Universidad de Cádiz) (acceptedVersion, cc-by-nc-nd)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Research Portal (King's College London) (submittedVersion, other-oa)
  • Amsterdam UMC (VU Amsterdam) - Institutional Repository (submittedVersion)
  • VU Research Portal (submittedVersion, other-oa)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
Funders
  • National Science Foundation
  • John Templeton Foundation
  • Eli Lilly and Company
  • Pfizer
  • South London and Maudsley NHS Foundation Trust
  • Maudsley Charity (TR130505)
  • National Institute for Health and Care Research
  • King's College London
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
  • Vrije Universiteit Amsterdam
  • Nederlandse Organisatie voor Wetenschappelijk Onderzoek (480- 05-003, VICI 453-14-005, NWO VICI 453-14-005, 453-14-005)
  • H. Lundbeck A/S
  • Medical Research Council (MR/M021475/1)
  • National Institute of Mental Health (U01MH109528, U01MH109536)
  • National Human Genome Research Institute
  • FP7 Ideas: European Research Council (295366)
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
intelligence, IQ, genetic loci, brain tissue expression, single-cell gene expression, pyramidal neurons, somatosensory cortex, hippocampal CA1, frontal cortex, intellectual disability
MeSH terms
Data Analysis, Brain, Cognition, Female, Frontal Lobe, Humans, Intelligence, Male, Temporal Lobe, Cohort Studies, Gene Expression, Pyramidal Cells, Genetic Predisposition to Disease, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Genetic Loci

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