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Cited by 71Genetic Associations and EpidemiologySchizophrenia research and treatmentGenetic Mapping and Diversity in Plants and Animals

Identification of Gene Loci That Overlap Between Schizophrenia and Educational Attainment

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Le Hellard, Stéphanie, Wang, Yunpeng, Witoelar, Aree, Zuber, Verena, Bettella, Francesco, Hugdahl, Kenneth, Espeseth, Thomas, Steen, Vidar M. +8 more·2016·Schizophrenia Bulletin
DOI 10.1093/schbul/sbw085PMC PMC5463752
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Abstract

There is evidence for genetic overlap between cognitive abilities and schizophrenia (SCZ), and genome-wide association studies (GWAS) demonstrate that both SCZ and general cognitive abilities have a strong polygenic component with many single-nucleotide polymorphisms (SNPs) each with a small effect. Here we investigated the shared genetic architecture between SCZ and educational attainment, which is regarded as a "proxy phenotype" for cognitive abilities, but may also reflect other traits. We applied a conditional false discovery rate (condFDR) method to GWAS of SCZ (n = 82 315), college completion ("College," n = 95 427), and years of education ("EduYears," n = 101 069). Variants associated with College or EduYears showed enrichment of association with SCZ, demonstrating polygenic overlap. This was confirmed by an increased replication rate in SCZ. By applying a condFDR threshold <0.01, we identified 18 genomic loci associated with SCZ after conditioning on College and 15 loci associated with SCZ after conditioning on EduYears. Ten of these loci overlapped. Using conjunctional FDR, we identified 10 loci shared between SCZ and College, and 29 loci shared between SCZ and EduYears. The majority of these loci had effects in opposite directions. Our results provide evidence for polygenic overlap between SCZ and educational attainment, and identify novel pleiotropic loci. Other studies have reported genetic overlap between SCZ and cognition, or SCZ and educational attainment, with negative correlation. Importantly, our methods enable identification of bi-directional effects, which highlight the complex relationship between SCZ and educational attainment, and support polygenic mechanisms underlying both cognitive dysfunction and creativity in SCZ.

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  • Previous reports support both a causal link and genetic overlap between intelligence and schizophrenia.

    “A number of previous reports support both a causal link and genetic overlap between these phenotypes 32,33”

    From Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence (2018) · cites this paper as [33]

    The Discussion and the ‘Genetic Overlap of SCZ and Educational Attainment’ section report genetic overlap between general cognition and schizophrenia; page numbers are unavailable in our copy. The paper does not establish a causal link between intelligence and schizophrenia, so it supports only the genetic-overlap part of the claim. (LLM, conf=0.88)

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Authors
Le Hellard, S., Wang, Y., Witoelar, A., Zuber, V., Bettella, F., Hugdahl, K., Espeseth, T., Steen, V. M., Melle, I., Desikan, R., Schork, A. J., Thompson, W. K., Dale, A. M., Djurovic, S., Andreassen, O. A., & Schizophrenia Working Group of the Psychiatric Genomics Consortium
Affiliations
  • Oslo University Hospital (NO)
  • Haukeland University Hospital (NO)
  • University of California San Diego (US)
ORCID
Venue
Schizophrenia Bulletin
Publisher
Oxford University Press (OUP)
Published
2016-06-23
Volume
43
Issue
3
Pages
sbw085
ISSN
  • 0586-7614 (ISSN-L)
  • 1745-1701
DOI
10.1093/schbul/sbw085
PMC
PMC5463752
OpenAlex
W2470044734
Cited by
71
References
2
Citations by year
2026: 1 · 2025: 3 · 2024: 4 · 2023: 5 · 2022: 10 · 2021: 7 · 2020: 10 · 2019: 13 · 2018: 7 · 2017: 9 · 2016: 2
FWCI
8.35
Type
journal article
Language
en
Open access
Locations
  • Schizophrenia Bulletin (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
  • Lancaster EPrints (Lancaster University) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • NOVA (University of Newcastle Australia) (submittedVersion)
Funders
National Institutes of Health (U54EB020403, T32 EB005970, R01AG031224, R01EB000790, RC2DA29475)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
Keywords
schizophrenia, educational attainment
MeSH terms
Adult, Aptitude, Educational Status, Female, Humans, Male, Schizophrenia, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Genetic Loci

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