title: Interplay between Schizophrenia Polygenic Risk Score and Childhood Adversity in First-Presentation Psychotic Disorder: A Pilot Study.
abstract: 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.
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
authors.forename: Antonella
authors.initials: A
authors.lastname: Trotta
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
authors.forename: Conrad
authors.initials: C
authors.lastname: Iyegbe
authors.affiliation: MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
authors.forename: Marta
authors.initials: M
authors.lastname: Di Forti
authors.affiliation: Department of Psychiatry, University of Hong Kong, Hong Kong, Special Administrative Region of China.|Centre for Genomic Sciences, University of Hong Kong, Hong Kong, Special Administrative Region of China.
authors.forename: Pak C
authors.initials: PC
authors.lastname: Sham
authors.affiliation: Department of Psychiatry, University of Hong Kong, Hong Kong, Special Administrative Region of China.|Centre for Genomic Sciences, University of Hong Kong, Hong Kong, Special Administrative Region of China.
authors.forename: Desmond D
authors.initials: DD
authors.lastname: Campbell
authors.affiliation: Department of Psychiatry, University of Hong Kong, Hong Kong, Special Administrative Region of China.|Centre for Genomic Sciences, University of Hong Kong, Hong Kong, Special Administrative Region of China.
authors.forename: Stacey S
authors.initials: SS
authors.lastname: Cherny
authors.affiliation: Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
authors.forename: Valeria
authors.initials: V
authors.lastname: Mondelli
authors.affiliation: MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.|Departments of Psychiatry and Medical Genetics, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Aitchison
authors.affiliation: Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
authors.forename: Robin M
authors.initials: RM
authors.lastname: Murray
authors.affiliation: MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Vassos
authors.affiliation: MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
authors.forename: Helen L
authors.initials: HL
authors.lastname: Fisher
mesh_terms: D000328:Adult; D000069586:Adult Survivors of Child Adverse Events / Q000523:psychology*; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D016678:Genome; D006801:Humans; D008297:Male; D020412:Multifactorial Inheritance; D010865:Pilot Projects; D011618:Psychotic Disorders / Q000175:diagnosis* / Q000235:genetics / Q000523:psychology; D018570:Risk Assessment; D012307:Risk Factors; D012559:Schizophrenia / Q000175:diagnosis* / Q000235:genetics; D055815:Young Adult