TY - JOUR

T1 - Polygenic Risk Scores, School Achievement, and Risk for Schizophrenia

T2 - A Danish Population-Based Study

AU - Sørensen, Holger J

AU - Debost, Jean-Christophe

AU - Agerbo, Esben

AU - Benros, Michael E

AU - McGrath, John J

AU - Mortensen, Preben Bo

AU - Ranning, Anne

AU - Hjorthøj, Carsten

AU - Mors, Ole

AU - Nordentoft, Merete

AU - Petersen, Liselotte

N1 - Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

U2 - 10.1016/j.biopsych.2018.04.012

DO - 10.1016/j.biopsych.2018.04.012

M3 - Journal article

C2 - 29807621

VL - 84

SP - 684

EP - 691

JO - Biological Psychiatry

JF - Biological Psychiatry

SN - 0006-3223

IS - 9

ER -