Department of Economics and Business Economics

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

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  • Holger J Sørensen, Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark; i-PSYCH initiative for Integrative Psychiatric Research, Lundbeck Foundation, Copenhagen. Electronic address: holger.jelling.soerensen@regionh.dk.
  • ,
  • Jean-Christophe Debost
  • Esben Agerbo
  • Michael E Benros, Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark; i-PSYCH initiative for Integrative Psychiatric Research, Lundbeck Foundation, Copenhagen.
  • ,
  • John J McGrath
  • Preben Bo Mortensen
  • Anne Ranning, Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark; i-PSYCH initiative for Integrative Psychiatric Research, Lundbeck Foundation, Copenhagen.
  • ,
  • Carsten Hjorthøj, Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark; i-PSYCH initiative for Integrative Psychiatric Research, Lundbeck Foundation, Copenhagen.
  • ,
  • Ole Mors
  • Merete Nordentoft, Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark; i-PSYCH initiative for Integrative Psychiatric Research, Lundbeck Foundation, Copenhagen.
  • ,
  • Liselotte Petersen

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.

Original languageEnglish
JournalBiological Psychiatry
Volume84
Issue9
Pages (from-to)684-691
Number of pages8
ISSN0006-3223
DOIs
Publication statusPublished - 2018

    Research areas

  • ADULT SCHIZOPHRENIA, AGE 16, BIPOLAR DISORDER, COHORT, EDUCATIONAL-ATTAINMENT, Epidemiology, GENOME-WIDE ASSOCIATION, Genetics, LOCI, MENTAL-ILLNESS, METAANALYSIS, PREMORBID INTELLIGENCE, Polygenic risk score, Register-based, Schizophrenia, School achievement

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