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Polygenic Risk Scores, School Achievement, and Risk for Schizophrenia: A Danish Population-Based Study

  • Holger J. Sørensen
    Correspondence
    Address correspondence to Holger J. Sørensen, M.D., Ph.D., Mental Health Centre Copenhagen & Copenhagen University, Kildegaardsvej 28, 4, 2900 Hellerup, Denmark.
    Affiliations
    Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark

    i-PSYCH initiative for Integrative Psychiatric Research, Lundbeck Foundation, Copenhagen, Denmark
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  • Jean-Christophe Debost
    Affiliations
    i-PSYCH initiative for Integrative Psychiatric Research, Lundbeck Foundation, Copenhagen, Denmark

    National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark

    Department of Psychosis, Aarhus University Hospital, Risskov, Denmark
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  • Esben Agerbo
    Affiliations
    i-PSYCH initiative for Integrative Psychiatric Research, Lundbeck Foundation, Copenhagen, Denmark

    National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark

    Centre for Integrated Register-Based Research and National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark
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  • Michael E. Benros
    Affiliations
    Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark

    i-PSYCH initiative for Integrative Psychiatric Research, Lundbeck Foundation, Copenhagen, Denmark
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  • John J. McGrath
    Affiliations
    National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark

    Queensland Brain Institute, University of Queensland, St Lucia, Australia
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  • Preben Bo Mortensen
    Affiliations
    i-PSYCH initiative for Integrative Psychiatric Research, Lundbeck Foundation, Copenhagen, Denmark

    National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark
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  • Anne Ranning
    Affiliations
    Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark

    i-PSYCH initiative for Integrative Psychiatric Research, Lundbeck Foundation, Copenhagen, Denmark
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  • Carsten Hjorthøj
    Affiliations
    Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark

    i-PSYCH initiative for Integrative Psychiatric Research, Lundbeck Foundation, Copenhagen, Denmark
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  • Ole Mors
    Affiliations
    i-PSYCH initiative for Integrative Psychiatric Research, Lundbeck Foundation, Copenhagen, Denmark

    Centre for Integrated Register-Based Research and National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark

    Department of Psychosis, Aarhus University Hospital, Risskov, Denmark
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  • Merete Nordentoft
    Affiliations
    Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark

    i-PSYCH initiative for Integrative Psychiatric Research, Lundbeck Foundation, Copenhagen, Denmark
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  • Liselotte Petersen
    Affiliations
    i-PSYCH initiative for Integrative Psychiatric Research, Lundbeck Foundation, Copenhagen, Denmark

    National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark

    Centre for Integrated Register-Based Research and National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark
    Search for articles by this author

      Abstract

      Background

      Studies have suggested that poor school achievement is associated with increased risk of schizophrenia; however, the possible genetic contribution to this association is unknown. We investigated the possible effect of the polygenic risk score (PRS) for schizophrenia (PRSSCZ) and for educational attainment (PRSEDU) on the association between school performance and later schizophrenia.

      Methods

      We conducted a case-cohort study on a Danish population-based sample born from 1987 to 1995 comprising 1470 individuals with schizophrenia and 7318 subcohort noncases. Genome-wide data, school performance, and family psychiatric and socioeconomic background information were obtained from national registers and neonatal biobanks. PRSSCZ and PRSEDU were calculated using discovery effect size estimates from a meta-analysis of 34,600 cases and 45,968 controls and 293,723 individuals.

      Results

      Higher PRSSCZ increased the risk (incidence rate ratio [IRR]: 1.28; 95% confidence interval [CI], 1.19–1.36), whereas higher PRSEDU decreased the risk of schizophrenia (IRR, 0.87; 95% CI, 0.82–0.92) per standard deviation. Not completing primary school and receiving low school marks were associated with increased risk of schizophrenia (IRR, 2.92; 95% CI, 2.37–3.60; and IRR, 1.58; 95% CI, 1.27–1.97, respectively), which was not confounded by PRSSCZ or PRSEDU. Adjusting for social factors and parental psychiatric history, effects of not completing primary school and receiving low school marks were attenuated by up to 25% (IRR, 2.19; 95% CI, 1.75–2.73; and IRR, 1.39; 95% CI, 1.11–1.75, respectively). Increasing PRSEDU correlated with better school performance (p < .01; R2 = 7.6%). PRSSCZ and PRSEDU was significantly negatively correlated (r = −.31, p < .01).

      Conclusions

      The current PRS did not account for the observed association between primary school performance and risk of schizophrenia.

      Keywords

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