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. 2014 Nov;40(6):1254-62.
doi: 10.1093/schbul/sbt146. Epub 2013 Oct 30.

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

Stanley Zammit  1 , Marian Hamshere  2 , Sarah Dwyer  2 , Lyudmila Georgiva  2 , Nic Timpson  3 , Valentina Moskvina  2 , Alexander Richards  2 , David M Evans  3 , Glyn Lewis  3 , Peter Jones  4 , Michael J Owen  2 , Michael C O'Donovan  2
Affiliations

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

Stanley Zammit et al. Schizophr Bull. 2014 Nov.

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.

Keywords: ALSPAC; GWAS; epidemiology; polygenic; psychosis; schizophrenia.

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Figures

Fig. 1.
Fig. 1.
Manhattan plot for the genome-wide association studies of definite psychotic experiences at ages 12 or 18. The Y-axis shows –Log (P values) of the logistic regression analysis (additive genetic model) for single nucleotide polymorphisms tested with definite psychotic experiences at ages 12 or 18 compared to none at both time points.
Fig. 2.
Fig. 2.
Q-Q plot for the genome-wide association studies of definite psychotic experiences at ages 12 or 18.
See this image and copyright information in PMC

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