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    Genome-wide analysis of adolescent psychotic-like experiences shows genetic overlap with psychiatric disorders

    Pain, O. and Dudbridge, F. and Cardno, A.G. and Freeman, D. and Yi, L. and Lundstrom, S. and Lichtenstein, P. and Ronald, Angelica (2018) Genome-wide analysis of adolescent psychotic-like experiences shows genetic overlap with psychiatric disorders. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 177 (4), pp. 416-425. ISSN 1552-4841.

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    Abstract

    This study aimed to test for overlap in genetic influences between psychotic-like experience traits shown by adolescents in the community, and clinically-recognized psychiatric disorders in adulthood, specifically schizophrenia, bipolar disorder, and major depression. The full spectra of psychotic-like experience domains, both in terms of their severity and type (positive, cognitive, and negative), were assessed using self- and parent-ratings in three European community samples aged 15-19 years (Final N incl. siblings = 6,297-10,098). A mega-genome-wide association study (mega-GWAS) for each psychotic-like experience domain was performed. SNP-heritability of each psychotic-like experience domain was estimated using genomic-relatedness-based restricted maximum-likelihood (GREML) and linkage disequilibrium- (LD-) score regression. Genetic overlap between specific psychotic-like experience domains and schizophrenia, bipolar disorder, and major depression was assessed using polygenic risk scoring (PRS) and LD-score regression. GREML returned SNP-heritability estimates of 3-9% for psychotic-like experience trait domains, with higher estimates for less skewed traits (Anhedonia, Cognitive Disorganization) than for more skewed traits (Paranoia and Hallucinations, Parent-rated Negative Symptoms). Mega-GWAS analysis identified one genome-wide significant association for Anhedonia within IDO2 but which did not replicate in an independent sample. PRS analysis revealed that the schizophrenia PRS significantly predicted all adolescent psychotic-like experience trait domains (Paranoia and Hallucinations only in non-zero scorers). The major depression PRS significantly predicted Anhedonia and Parent-rated Negative Symptoms in adolescence. Psychotic-like experiences during adolescence in the community show additive genetic effects and partly share genetic influences with clinically-recognized psychiatric disorders, specifically schizophrenia and major depression.

    Metadata

    Item Type: Article
    Additional Information: This is the peer reviewed version of the article, which has been published in final form at the link above. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
    Keyword(s) / Subject(s): Adolescence, Psychotic-like experiences, Schizophrenia, ALSPAC, GWAS
    School: Birkbeck Schools and Departments > School of Science > Psychological Sciences
    Depositing User: Angelica Ronald
    Date Deposited: 02 Mar 2018 09:34
    Last Modified: 13 Sep 2019 15:39
    URI: http://eprints.bbk.ac.uk/id/eprint/21446

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