Holger J Sørensen1, Jean-Christophe Debost2, Esben Agerbo3, Michael E Benros4, John J McGrath5, Preben Bo Mortensen6, Anne Ranning4, Carsten Hjorthøj4, Ole Mors7, Merete Nordentoft4, Liselotte Petersen3. 1. Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark; i-PSYCH initiative for Integrative Psychiatric Research, Lundbeck Foundation, Copenhagen, Denmark. Electronic address: holger.jelling.soerensen@regionh.dk. 2. 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. 3. 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. 4. Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark; i-PSYCH initiative for Integrative Psychiatric Research, Lundbeck Foundation, Copenhagen, Denmark. 5. National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark; Queensland Brain Institute, University of Queensland, St Lucia, Australia. 6. i-PSYCH initiative for Integrative Psychiatric Research, Lundbeck Foundation, Copenhagen, Denmark; National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark. 7. 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.
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.
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.
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