A population-based study of genetic variation and psychotic experiences in adolescents

Zammit, Stanley ORCID: https://orcid.org/0000-0002-2647-9211, Hamshere, Marian L. ORCID: https://orcid.org/0000-0002-8990-0958, Dwyer, Sarah Lynne, Georgiva, Lyudmila, Timpson, Nic, Escott-Price, Valentina ORCID: https://orcid.org/0000-0003-1784-5483, Richards, Alexander, Evans, David M., Lewis, Glyn, Jones, Peter, Owen, Michael John ORCID: https://orcid.org/0000-0003-4798-0862 and O'Donovan, Michael Conlon ORCID: https://orcid.org/0000-0001-7073-2379 2013. A population-based study of genetic variation and psychotic experiences in adolescents. Schizophrenia Bulletin 40 (6) , pp. 1254-1262. 10.1093/schbul/sbt146

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Medicine Neuroscience and Mental Health Research Institute (NMHRI)
Subjects:	Q Science > QH Natural history > QH426 Genetics R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Additional Information:	Cardiff OA ref: OA-20132014-37
Publisher:	Oxford University Press
ISSN:	0586-7614
Funders:	Medical Research Council
Date of First Compliant Deposit:	30 March 2016
Last Modified:	05 May 2023 23:11
URI:	https://orca.cardiff.ac.uk/id/eprint/56585

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