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Genetic overlap between psychotic experiences in the community across age and with psychiatric disorders

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posted on 28.04.2020, 08:52 by Wikus Barkhuizen, Oliver Pain, Frank Dudbridge, Angelica Ronald
This study explores the degree to which genetic influences on psychotic experiences are stable across adolescence and adulthood, and their overlap with psychiatric disorders. Genome-wide association results were obtained for adolescent psychotic experiences and negative symptom traits (N = 6297–10,098), schizotypy (N = 3967–4057) and positive psychotic experiences in adulthood (N = 116,787–117,794), schizophrenia (N = 150,064), bipolar disorder (N = 41,653), and depression (N = 173,005). Linkage disequilibrium score regression was used to estimate genetic correlations. Implicated genes from functional and gene-based analyses were compared. Mendelian randomization was performed on trait pairs with significant genetic correlations. Results indicated that subclinical auditory and visual hallucinations and delusions of persecution during adulthood were significantly genetically correlated with schizophrenia (rg = 0.27–0.67) and major depression (rg = 0.41–96) after correction for multiple testing. Auditory and visual subclinical hallucinations were highly genetically correlated (rg = 0.95). Cross-age genetic correlations for psychotic experiences were not significant. Gene mapping and association analyses revealed 14 possible genes associated with psychotic experiences that overlapped across age for psychotic experiences or between psychotic experiences and psychiatric disorders. Mendelian randomization indicated bidirectional associations between auditory and visual hallucinations in adults but did not support causal relationships between psychotic experiences and psychiatric disorders. These findings indicate that psychotic experiences in adulthood may be more linked genetically to schizophrenia and major depression than psychotic experiences in adolescence. Our study implicated specific genes that are associated with psychotic experiences across development, as well as genes shared between psychotic experiences and psychiatric disorders.


This work was supported by the UK Medical Research Council (G1100559 to A.R.) and a Wellcome Trust ISSF grant (204770/Z/16/Z) to W.B. W.B. is funded by the Camara-Rijvers David Studentship. We acknowledge the ongoing contribution of the participants in the TEDS and their families, the ALSPAC, the CATSS, and those who participated in the NFBC and in the UK Biobank. We thank the funding bodies and research teams, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses. TEDS is supported by a program grant to Robert Plomin from the UK Medical Research Council (MR/M021475/1). The UK Medical Research Council and Wellcome (Grant ref: 102215/2/13/2) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors, and W.B. and A.R. will serve as guarantors for the contents of this paper. ALSPAC GWAS data were generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. We are grateful to Neale Lab and the Psychiatric Genomics Consortium (PGC) for their contributions in providing the genetic summary results used in this study, and to Dr W. Hennah and A. Ortega-Alonso for preparing and sharing the schizotypy summary statistics.



Barkhuizen, W., Pain, O., Dudbridge, F. et al. Genetic overlap between psychotic experiences in the community across age and with psychiatric disorders. Transl Psychiatry 10, 86 (2020). https://doi.org/10.1038/s41398-020-0765-2


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A preprint of this manuscript was posted to bioRxiv, 718015. doi:10.1101/718015.