Interplay between schizophrenia polygenic risk score and childhood adversity in first-presentation psychotic disorder: a pilot study

Trotta, A. et al. (2016) Interplay between schizophrenia polygenic risk score and childhood adversity in first-presentation psychotic disorder: a pilot study. PLoS ONE, 11(9), e0163319. (doi: 10.1371/journal.pone.0163319) (PMID:27648571) (PMCID:PMC5029892)

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A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to number or severity of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing genetic vulnerability. Research on gene-environment interaction in psychosis has primarily focused on candidate genes, although the genetic effects are now known to be polygenic. This pilot study investigated whether the effect of childhood adversity on psychosis is moderated by the polygenic risk score for schizophrenia (PRS). Data were utilised from the Genes and Psychosis (GAP) study set in South London, UK. The GAP sample comprises 285 first-presentation psychosis cases and 256 unaffected controls with information on childhood adversity. We studied only white subjects (80 cases and 110 controls) with PRS data, as the PRS has limited predictive ability in patients of African ancestry. The occurrence of childhood adversity was assessed with the Childhood Experience of Care and Abuse Questionnaire (CECA.Q) and the PRS was based on genome-wide meta-analysis results for schizophrenia from the Psychiatric Genomics Consortium. Higher schizophrenia PRS and childhood adversities each predicted psychosis status. Nevertheless, no evidence was found for interaction as departure from additivity, indicating that the effect of polygenic risk scores on psychosis was not increased in the presence of a history of childhood adversity. These findings are compatible with a multifactorial threshold model in which both genetic liability and exposure to environmental risk contribute independently to the etiology of psychosis.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Campbell, Dr Desmond
Authors: Trotta, A., Iyegbe, C., Di Forti, M., Sham, P. C., Campbell, D. D., Cherny, S. S., Mondelli, V., Aitchison, K. J., Murray, R. M., Vassos, E., and Fisher, H. L.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN (Online):1932-6203
Copyright Holders:Copyright © 2016 The AuthorTrotta et al.
First Published:First published in PLoS ONE 11(9):e0163319
Publisher Policy:Reproduced under a Creative Commons License

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