Schizophrenia polygenic risk is associated with child mental health problems through early childhood adversity: evidence for a gene-environment correlation.

Autor: Bolhuis K; Department of Child and Adolescent Psychiatry, Erasmus Medical Center, Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands., Steenkamp LR; Department of Child and Adolescent Psychiatry, Erasmus Medical Center, Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands.; Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands., Blanken LME; Department of Child and Adolescent Psychiatry, Erasmus Medical Center, Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands., Neumann A; Department of Child and Adolescent Psychiatry, Erasmus Medical Center, Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands.; Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC, Canada., Jansen PR; Department of Child and Adolescent Psychiatry, Erasmus Medical Center, Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands.; Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, VU University, Amsterdam, The Netherlands.; Department of Clinical Genetics, Amsterdam University Medical Centre, Location VUmc, Amsterdam, The Netherlands., Hillegers MHJ; Department of Child and Adolescent Psychiatry, Erasmus Medical Center, Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands., Cecil CAM; Department of Child and Adolescent Psychiatry, Erasmus Medical Center, Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands.; Department of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands.; Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Center, 2333 ZC, Leiden, The Netherlands., Tiemeier H; Department of Child and Adolescent Psychiatry, Erasmus Medical Center, Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands. tiemeier@hsph.harvard.edu.; Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Kresge Building, Room 619, 677 Huntington Avenue, Boston, MA, USA. tiemeier@hsph.harvard.edu., Kushner SA; Department of Psychiatry, Erasmus University Medical Center, Rotterdam, The Netherlands.
Jazyk: angličtina
Zdroj: European child & adolescent psychiatry [Eur Child Adolesc Psychiatry] 2022 Mar; Vol. 31 (3), pp. 529-539. Date of Electronic Publication: 2021 Feb 26.
DOI: 10.1007/s00787-021-01727-4
Abstrakt: Previous studies have shown that schizophrenia polygenic risk predicts a multitude of mental health problems in the general population. Yet it is unclear by which mechanisms these associations arise. Here, we explored a possible gene-environment correlation in the association of schizophrenia polygenic risk with mental health problems via childhood adversity. This study was embedded in the population-based Generation R Study, including N = 1901 participants with genotyping for schizophrenia polygenic risk, maternal reporting of childhood adversity, and Child Behaviour Checklist measurement of mental health problems. Independent replication was attempted in the Avon Longitudinal Study of Parents and Children (ALSPAC; N = 3641). Associations were analysed with Poisson regression and statistical mediation analysis. Higher burden of schizophrenia polygenic risk was associated with greater exposure to childhood adversity (P-value threshold < 0.5: Generation R Study, OR = 1.08, 95%CI 1.02-1.15, P = 0.01; ALSPAC, OR = 1.02, 95%CI 1.01-1.03, P < 0.01). Childhood adversities partly explained the relationship of schizophrenia polygenic risk with emotional, attention, and thought problems (proportion explained, range 5-23%). Direct effects of schizophrenia polygenic risk and adversity on mental health outcomes were also observed. In summary, genetic liability to schizophrenia increased the risk for mental health problems in the general paediatric population through childhood adversity. Although this finding could result from a mediated causal relationship between genotype and mental health, we argue that these observations most likely reflect a gene-environment correlation, i.e. adversities are a marker for the genetic risk that parents transmit to children. These and similar recent findings raise important conceptual questions about preventative interventions aimed at reducing childhood adversities.
(© 2021. The Author(s).)
Databáze: MEDLINE
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