title: A population-based study of genetic variation and psychotic experiences in adolescents.
abstract: Psychotic experiences are not uncommon in general population samples, but no studies have examined to what extent confirmed risk variants for schizophrenia are associated with such experiences. A total of 3483 children in a birth cohort study participated in semistructured interviews for psychotic experiences at ages 12 and 18. We examined whether (1) a composite measure of risk for schizophrenia conferred by common alleles (polygenic score) was associated with psychotic experiences, (2) variants with genome-wide evidence for association with schizophrenia were associated with psychotic experiences, and (3) we could identify genetic variants for psychotic experiences using a genome-wide association (GWA) approach. We found no evidence that a schizophrenia polygenic score, or variants showing genome-wide evidence of association with schizophrenia, were associated with adolescent psychotic experiences within the general population. In fact, individuals who had a higher number of risk alleles for genome-wide hits for schizophrenia showed a decreased risk of psychotic experiences. In the GWA study, no variants showed GWA for psychotic experiences, and there was no evidence that the strongest hits (P < 5 × 10(-5)) were enriched for variants associated with schizophrenia in large consortia. Although polygenic scores are weak tools for prediction of schizophrenia, they show strong evidence of association with this disorder. Our findings, however, lend little support to the hypothesis that psychotic experiences in population-based samples of adolescents share a comparable genetic architecture to schizophrenia, or that utilizing a broader and more common phenotype of psychotic experiences will be an efficient approach to increase understanding of the genetic etiology of schizophrenia.
authors.affiliation: Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK; Centre for Academic Mental Health, School of Social and Community Medicine, University of Bristol, Bristol, UK; zammits@cardiff.ac.uk.
authors.forename: Stanley
authors.initials: S
authors.lastname: Zammit
authors.affiliation: Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK;
authors.forename: Marian
authors.initials: M
authors.lastname: Hamshere
authors.affiliation: Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK;
authors.forename: Sarah
authors.initials: S
authors.lastname: Dwyer
authors.affiliation: Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK;
authors.forename: Lyudmila
authors.initials: L
authors.lastname: Georgiva
authors.affiliation: Centre for Academic Mental Health, School of Social and Community Medicine, University of Bristol, Bristol, UK;
authors.forename: Nic
authors.initials: N
authors.lastname: Timpson
authors.affiliation: Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK;
authors.forename: Valentina
authors.initials: V
authors.lastname: Moskvina
authors.affiliation: Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK;
authors.forename: Alexander
authors.initials: A
authors.lastname: Richards
authors.affiliation: Centre for Academic Mental Health, School of Social and Community Medicine, University of Bristol, Bristol, UK;
authors.forename: David M
authors.initials: DM
authors.lastname: Evans
authors.affiliation: Centre for Academic Mental Health, School of Social and Community Medicine, University of Bristol, Bristol, UK;
authors.forename: Glyn
authors.initials: G
authors.lastname: Lewis
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Jones
authors.affiliation: Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK;
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owen
authors.affiliation: Institute of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK;
authors.forename: Michael C
authors.initials: MC
authors.lastname: O'Donovan
mesh_terms: D000293:Adolescent; D002648:Child; D004739:England / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D020412:Multifactorial Inheritance; D011618:Psychotic Disorders / Q000453:epidemiology / Q000235:genetics*; D012306:Risk; D012559:Schizophrenia / Q000453:epidemiology / Q000235:genetics*
keywords: ALSPAC; GWAS; epidemiology; polygenic; psychosis; schizophrenia