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Genome-wide association study results for educational attainment aid in identifying genetic heterogeneity of schizophrenia

Author

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  • V. Bansal

    (Max Planck Institute of Experimental Medicine
    German Center for Neurodegenerative Diseases (DZNE)
    University Clinic Hamburg-Eppendorf)

  • M. Mitjans

    (Max Planck Institute of Experimental Medicine
    DFG Research Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB))

  • C. A. P. Burik

    (Vrije Universiteit Amsterdam
    Erasmus University Rotterdam
    School of Business and Economics, Department of Economics)

  • R. K. Linnér

    (Vrije Universiteit Amsterdam
    Erasmus University Rotterdam
    School of Business and Economics, Department of Economics)

  • A. Okbay

    (Vrije Universiteit Amsterdam
    School of Business and Economics, Department of Economics)

  • C. A. Rietveld

    (Erasmus University Rotterdam
    Erasmus University Rotterdam)

  • M. Begemann

    (Max Planck Institute of Experimental Medicine
    University of Göttingen)

  • S. Bonn

    (German Center for Neurodegenerative Diseases (DZNE)
    University Clinic Hamburg-Eppendorf)

  • S. Ripke

    (Massachusetts General Hospital
    Broad Institute of MIT and Harvard
    Charité-Universitätsmedizin Berlin, Campus Mitte)

  • R. Vlaming

    (Vrije Universiteit Amsterdam
    School of Business and Economics, Department of Economics)

  • M. G. Nivard

    (Vrije Universiteit Amsterdam)

  • H. Ehrenreich

    (Max Planck Institute of Experimental Medicine
    DFG Research Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB))

  • P. D. Koellinger

    (Vrije Universiteit Amsterdam
    Erasmus University Rotterdam
    School of Business and Economics, Department of Economics)

Abstract

Higher educational attainment (EA) is negatively associated with schizophrenia (SZ). However, recent studies found a positive genetic correlation between EA and SZ. We investigate possible causes of this counterintuitive finding using genome-wide association study results for EA and SZ (N = 443,581) and a replication cohort (1169 controls; 1067 cases) with deeply phenotyped SZ patients. We find strong genetic dependence between EA and SZ that cannot be explained by chance, linkage disequilibrium, or assortative mating. Instead, several genes seem to have pleiotropic effects on EA and SZ, but without a clear pattern of sign concordance. Using EA as a proxy phenotype, we isolate FOXO6 and SLITRK1 as novel candidate genes for SZ. Our results reveal that current SZ diagnoses aggregate over at least two disease subtypes: one part resembles high intelligence and bipolar disorder (BIP), while the other part is a cognitive disorder that is independent of BIP.

Suggested Citation

  • V. Bansal & M. Mitjans & C. A. P. Burik & R. K. Linnér & A. Okbay & C. A. Rietveld & M. Begemann & S. Bonn & S. Ripke & R. Vlaming & M. G. Nivard & H. Ehrenreich & P. D. Koellinger, 2018. "Genome-wide association study results for educational attainment aid in identifying genetic heterogeneity of schizophrenia," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05510-z
    DOI: 10.1038/s41467-018-05510-z
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    Cited by:

    1. Mitchell, Brittany L. & Hansell, Narelle K. & McAloney, Kerrie & Martin, Nicholas G. & Wright, Margaret J. & Renteria, Miguel E. & Grasby, Katrina L., 2022. "Polygenic influences associated with adolescent cognitive skills," Intelligence, Elsevier, vol. 94(C).
    2. Max Lam & Chia-Yen Chen & W. David Hill & Charley Xia & Ruoyu Tian & Daniel F. Levey & Joel Gelernter & Murray B. Stein & Alexander S. Hatoum & Hailiang Huang & Anil K. Malhotra & Heiko Runz & Tian Ge, 2022. "Collective genomic segments with differential pleiotropic patterns between cognitive dimensions and psychopathology," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    3. Cornelius A. Rietveld & Eric A.W. Slob & A. Roy Thurik, 2021. "A decade of research on the genetics of entrepreneurship: a review and view ahead," Small Business Economics, Springer, vol. 57(3), pages 1303-1317, October.

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