Are genetic risk factors for psychosis also associated with dimension-specific psychotic experiences in adolescence?
Psychosis has been hypothesised to be a continuously distributed quantitative phenotype and disorders such as schizophrenia and bipolar disorder represent its extreme manifestations. Evidence suggests that common genetic variants play an important role in liability to both schizophrenia and bipolar...
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0094398&type=printable |
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| author | Dominika Sieradzka Robert A Power Daniel Freeman Alastair G Cardno Philip McGuire Robert Plomin Emma L Meaburn Frank Dudbridge Angelica Ronald |
| author_facet | Dominika Sieradzka Robert A Power Daniel Freeman Alastair G Cardno Philip McGuire Robert Plomin Emma L Meaburn Frank Dudbridge Angelica Ronald |
| author_sort | Dominika Sieradzka |
| collection | DOAJ |
| description | Psychosis has been hypothesised to be a continuously distributed quantitative phenotype and disorders such as schizophrenia and bipolar disorder represent its extreme manifestations. Evidence suggests that common genetic variants play an important role in liability to both schizophrenia and bipolar disorder. Here we tested the hypothesis that these common variants would also influence psychotic experiences measured dimensionally in adolescents in the general population. Our aim was to test whether schizophrenia and bipolar disorder polygenic risk scores (PRS), as well as specific single nucleotide polymorphisms (SNPs) previously identified as risk variants for schizophrenia, were associated with adolescent dimension-specific psychotic experiences. Self-reported Paranoia, Hallucinations, Cognitive Disorganisation, Grandiosity, Anhedonia, and Parent-rated Negative Symptoms, as measured by the Specific Psychotic Experiences Questionnaire (SPEQ), were assessed in a community sample of 2,152 16-year-olds. Polygenic risk scores were calculated using estimates of the log of odds ratios from the Psychiatric Genomics Consortium GWAS stage-1 mega-analysis of schizophrenia and bipolar disorder. The polygenic risk analyses yielded no significant associations between schizophrenia and bipolar disorder PRS and the SPEQ measures. The analyses on the 28 individual SNPs previously associated with schizophrenia found that two SNPs in TCF4 returned a significant association with the SPEQ Paranoia dimension, rs17512836 (p-value = 2.57×10⁻⁴) and rs9960767 (p-value = 6.23×10⁻⁴). Replication in an independent sample of 16-year-olds (N = 3,427) assessed using the Psychotic-Like Symptoms Questionnaire (PLIKS-Q), a composite measure of multiple positive psychotic experiences, failed to yield significant results. Future research with PRS derived from larger samples, as well as larger adolescent validation samples, would improve the predictive power to test these hypotheses further. The challenges of relating adult clinical diagnostic constructs such as schizophrenia to adolescent psychotic experiences at a genetic level are discussed. |
| format | Article |
| id | doaj-art-abec6940bf034b79ba017ffbed07869e |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-abec6940bf034b79ba017ffbed07869e2025-08-20T02:34:10ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0194e9439810.1371/journal.pone.0094398Are genetic risk factors for psychosis also associated with dimension-specific psychotic experiences in adolescence?Dominika SieradzkaRobert A PowerDaniel FreemanAlastair G CardnoPhilip McGuireRobert PlominEmma L MeaburnFrank DudbridgeAngelica RonaldPsychosis has been hypothesised to be a continuously distributed quantitative phenotype and disorders such as schizophrenia and bipolar disorder represent its extreme manifestations. Evidence suggests that common genetic variants play an important role in liability to both schizophrenia and bipolar disorder. Here we tested the hypothesis that these common variants would also influence psychotic experiences measured dimensionally in adolescents in the general population. Our aim was to test whether schizophrenia and bipolar disorder polygenic risk scores (PRS), as well as specific single nucleotide polymorphisms (SNPs) previously identified as risk variants for schizophrenia, were associated with adolescent dimension-specific psychotic experiences. Self-reported Paranoia, Hallucinations, Cognitive Disorganisation, Grandiosity, Anhedonia, and Parent-rated Negative Symptoms, as measured by the Specific Psychotic Experiences Questionnaire (SPEQ), were assessed in a community sample of 2,152 16-year-olds. Polygenic risk scores were calculated using estimates of the log of odds ratios from the Psychiatric Genomics Consortium GWAS stage-1 mega-analysis of schizophrenia and bipolar disorder. The polygenic risk analyses yielded no significant associations between schizophrenia and bipolar disorder PRS and the SPEQ measures. The analyses on the 28 individual SNPs previously associated with schizophrenia found that two SNPs in TCF4 returned a significant association with the SPEQ Paranoia dimension, rs17512836 (p-value = 2.57×10⁻⁴) and rs9960767 (p-value = 6.23×10⁻⁴). Replication in an independent sample of 16-year-olds (N = 3,427) assessed using the Psychotic-Like Symptoms Questionnaire (PLIKS-Q), a composite measure of multiple positive psychotic experiences, failed to yield significant results. Future research with PRS derived from larger samples, as well as larger adolescent validation samples, would improve the predictive power to test these hypotheses further. The challenges of relating adult clinical diagnostic constructs such as schizophrenia to adolescent psychotic experiences at a genetic level are discussed.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0094398&type=printable |
| spellingShingle | Dominika Sieradzka Robert A Power Daniel Freeman Alastair G Cardno Philip McGuire Robert Plomin Emma L Meaburn Frank Dudbridge Angelica Ronald Are genetic risk factors for psychosis also associated with dimension-specific psychotic experiences in adolescence? PLoS ONE |
| title | Are genetic risk factors for psychosis also associated with dimension-specific psychotic experiences in adolescence? |
| title_full | Are genetic risk factors for psychosis also associated with dimension-specific psychotic experiences in adolescence? |
| title_fullStr | Are genetic risk factors for psychosis also associated with dimension-specific psychotic experiences in adolescence? |
| title_full_unstemmed | Are genetic risk factors for psychosis also associated with dimension-specific psychotic experiences in adolescence? |
| title_short | Are genetic risk factors for psychosis also associated with dimension-specific psychotic experiences in adolescence? |
| title_sort | are genetic risk factors for psychosis also associated with dimension specific psychotic experiences in adolescence |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0094398&type=printable |
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