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.
Highlights
The public health burden caused by schizophrenia and other psychotic disorders is a strong driver for research aimed at understanding the biological mechanisms underlying etiology that might potentially impact upon development of novel treatments
This study examines data from 3483 children from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort who (1) participated in the PsychosisLike Symptoms interviews (PLIKSi) when they were aged 12 (N = 6796) and 18 years (N = 4724) and (2) had genetic data available
On average, individuals with definite psychotic experiences had higher polygenic scores than those without, there was, at best, only very weak evidence that this was different from random variation
Summary
The public health burden caused by schizophrenia and other psychotic disorders is a strong driver for research aimed at understanding the biological mechanisms underlying etiology that might potentially impact upon development of novel treatments. Recent findings from genome-wide association studies (GWAS) and genome-wide studies of copy number variation provide strong evidence, implicating a number of genetic loci as risk factors for schizophrenia.[8] There is increasing evidence of shared genetic contribution across different psychotic disorders, with most research based on GWAS data focusing on the overlap between schizophrenia and bipolar disorder.[8,9,10] For example, a composite measure of risk conferred by common alleles (known as a polygenic score) derived from a discovery schizophrenia sample has been shown to successfully discriminate individuals with schizophrenia, and with bipolar disorder, in other samples.[11]
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