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 Faculties and Schools > Faculty of Science > School of Psychological Sciences |
| Depositing User: | Angelica Ronald |
| Date Deposited: | 02 Mar 2018 09:34 |
| Last Modified: | 02 Aug 2023 17:39 |
| URI: | https://eprints.bbk.ac.uk/id/eprint/21446 |
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