title: An Examination of Polygenic Score Risk Prediction in Individuals With First-Episode Psychosis.
abstract: Polygenic risk scores (PRSs) have successfully summarized genome-wide effects of genetic variants in schizophrenia with significant predictive power. In a clinical sample of first-episode psychosis (FEP) patients, we estimated the ability of PRSs to discriminate case-control status and to predict the development of schizophrenia as opposed to other psychoses.
  
  
  
  The sample (445 case and 265 control subjects) was genotyped on the Illumina HumanCore Exome BeadChip with an additional 828 control subjects of African ancestry genotyped on the Illumina Multi-Ethnic Genotyping Array. To calculate PRSs, we used the results from the latest Psychiatric Genomics Consortium schizophrenia meta-analysis. We examined the association of PRSs with case-control status and with schizophrenia versus other psychoses in European and African ancestry FEP patients and in a second sample of 248 case subjects with chronic psychosis.
  
  
  
  PRS had good discriminative ability of case-control status in FEP European ancestry individuals (9.4% of the variance explained, p < 10-6), but lower in individuals of African ancestry (R2= 1.1%, p = .004). Furthermore, PRS distinguished European ancestry case subjects who went on to acquire a schizophrenia diagnosis from those who developed other psychotic disorders (R2= 9.2%, p = .002).
  
  
  
  PRS was a powerful predictor of case-control status in a European sample of patients with FEP, even though a large proportion did not have an established diagnosis of schizophrenia at the time of assessment. PRS was significantly different between those case subjects who developed schizophrenia from those who did not, although the discriminative accuracy may not yet be sufficient for clinical utility in FEP.
authors.affiliation: Medical Research Council, Social, Genetic & Developmental Psychiatry Centre; Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom. Electronic address: evangelos.vassos@kcl.ac.uk.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Vassos
authors.affiliation: Medical Research Council, Social, Genetic & Developmental Psychiatry Centre; Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; Departments of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
authors.forename: Marta
authors.initials: M
authors.lastname: Di Forti
authors.affiliation: Medical Research Council, Social, Genetic & Developmental Psychiatry Centre; Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Coleman
authors.affiliation: Departments 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: Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Diana
authors.initials: D
authors.lastname: Prata
authors.affiliation: Medical Research Council, Social, Genetic & Developmental Psychiatry Centre; Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
authors.forename: Jack
authors.initials: J
authors.lastname: Euesden
authors.affiliation: Medical Research Council, Social, Genetic & Developmental Psychiatry Centre; Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: O'Reilly
authors.affiliation: Medical Research Council, Social, Genetic & Developmental Psychiatry Centre; Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; National Institute for Health Research Mental Health Biomedical Research Centre, South London and Maudsley National Health Service Foundation Trust and King's College London, London, United Kingdom.
authors.forename: Charles
authors.initials: C
authors.lastname: Curtis
authors.affiliation: Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
authors.forename: Anna
authors.initials: A
authors.lastname: Kolliakou
authors.affiliation: Medical Research Council, Social, Genetic & Developmental Psychiatry Centre; Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; National Institute for Health Research Mental Health Biomedical Research Centre, South London and Maudsley National Health Service Foundation Trust and King's College London, London, United Kingdom.
authors.forename: Hamel
authors.initials: H
authors.lastname: Patel
authors.affiliation: Medical Research Council, Social, Genetic & Developmental Psychiatry Centre; Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; National Institute for Health Research Mental Health Biomedical Research Centre, South London and Maudsley National Health Service Foundation Trust and King's College London, London, United Kingdom.
authors.forename: Stephen
authors.initials: S
authors.lastname: Newhouse
authors.affiliation: Department of Medical and Molecular Genetics, King's College London, London, United Kingdom.
authors.forename: Matthew
authors.initials: M
authors.lastname: Traylor
authors.affiliation: Departments of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
authors.forename: Olesya
authors.initials: O
authors.lastname: Ajnakina
authors.affiliation: Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Valeria
authors.initials: V
authors.lastname: Mondelli
authors.affiliation: Departments of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
authors.forename: Tiago Reis
authors.initials: TR
authors.lastname: Marques
authors.affiliation: Departments of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
authors.forename: Poonam
authors.initials: P
authors.lastname: Gardner-Sood
authors.affiliation: Medical Research Council, Social, Genetic & Developmental Psychiatry Centre; Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; Department of Psychiatry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Aitchison
authors.affiliation: Basic and Clinical Neuroscience; Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Powell
authors.affiliation: Departments of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
authors.forename: Zerrin
authors.initials: Z
authors.lastname: Atakan
authors.affiliation: School of Psychology, University of Sussex, Brighton and Sussex Partnership National Health Service Foundation Trust, West Sussex.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Greenwood
authors.affiliation: Departments of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; South London and Maudsley National Health Service Foundation Trust, London; United Kingdom.
authors.forename: Shubulade
authors.initials: S
authors.lastname: Smith
authors.affiliation: Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
authors.forename: Khalida
authors.initials: K
authors.lastname: Ismail
authors.affiliation: Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
authors.forename: Carmine
authors.initials: C
authors.lastname: Pariante
authors.affiliation: Departments of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
authors.forename: Fiona
authors.initials: F
authors.lastname: Gaughran
authors.affiliation: Departments of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; National Institute for Health Research Mental Health Biomedical Research Centre, South London and Maudsley National Health Service Foundation Trust and King's College London, London, United Kingdom.
authors.forename: Paola
authors.initials: P
authors.lastname: Dazzan
authors.affiliation: Department of Clinical Neurosciences, Neurology Unit, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Hugh S
authors.initials: HS
authors.lastname: Markus
authors.affiliation: Departments of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
authors.forename: Anthony S
authors.initials: AS
authors.lastname: David
authors.affiliation: Medical Research Council, Social, Genetic & Developmental Psychiatry Centre; Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
authors.forename: Cathryn M
authors.initials: CM
authors.lastname: Lewis
authors.affiliation: Departments 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: Medical Research Council, Social, Genetic & Developmental Psychiatry Centre; Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom; National Institute for Health Research Mental Health Biomedical Research Centre, South London and Maudsley National Health Service Foundation Trust and King's College London, London, United Kingdom.
authors.forename: Gerome
authors.initials: G
authors.lastname: Breen
mesh_terms: D000328:Adult; D044383:Black People / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D020412:Multifactorial Inheritance; D011618:Psychotic Disorders / Q000175:diagnosis / Q000235:genetics*; D012307:Risk Factors; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics*; D044465:White People / Q000235:genetics; D055815:Young Adult
keywords: GWAS; Genetics; Polygenic score; Psychosis; Risk prediction; Schizophrenia