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 - 2018/11/1
Y1 - 2018/11/1
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
SN - 0006-3223
VL - 84
SP - 684
EP - 691
JO - Biological Psychiatry
JF - Biological Psychiatry
IS - 9
ER -