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Investigation of the genetic association between quantitative measures of psychosis and schizophrenia: A polygenic risk score analysis

Derks, Eske M., Vorstman, Jacob A. S., Ripke, Stephan, Kahn, Rene S., Ophoff, Roel A., Craddock, Nicholas John ORCID: https://orcid.org/0000-0003-2171-0610, Escott-Price, Valentina ORCID: https://orcid.org/0000-0003-1784-5483, Hamshere, Marian Lindsay ORCID: https://orcid.org/0000-0002-8990-0958, Holmans, Peter Alan ORCID: https://orcid.org/0000-0003-0870-9412, Kirov, George ORCID: https://orcid.org/0000-0002-3427-3950, O'Donovan, Michael Conlon ORCID: https://orcid.org/0000-0001-7073-2379, Owen, Michael John ORCID: https://orcid.org/0000-0003-4798-0862 and Zammit, Stanley ORCID: https://orcid.org/0000-0002-2647-9211 2012. Investigation of the genetic association between quantitative measures of psychosis and schizophrenia: A polygenic risk score analysis. PLoS ONE 7 (6) , e37852. 10.1371/journal.pone.0037852

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Abstract

The presence of subclinical levels of psychosis in the general population may imply that schizophrenia is the extreme expression of more or less continuously distributed traits in the population. In a previous study, we identified five quantitative measures of schizophrenia (positive, negative, disorganisation, mania, and depression scores). The aim of this study is to examine the association between a direct measure of genetic risk of schizophrenia and the five quantitative measures of psychosis. Estimates of the log of the odds ratios of case/control allelic association tests were obtained from the Psychiatric GWAS Consortium (PGC) (minus our sample) which included genome-wide genotype data of 8,690 schizophrenia cases and 11,831 controls. These data were used to calculate genetic risk scores in 314 schizophrenia cases and 148 controls from the Netherlands for whom genotype data and quantitative symptom scores were available. The genetic risk score of schizophrenia was significantly associated with case-control status (p<0.0001). In the case-control sample, the five psychosis dimensions were found to be significantly associated with genetic risk scores; the correlations ranged between.15 and.27 (all p<.001). However, these correlations were not significant in schizophrenia cases or controls separately. While this study confirms the presence of a genetic risk for schizophrenia as categorical diagnostic trait, we did not find evidence for the genetic risk underlying quantitative schizophrenia symptom dimensions. This does not necessarily imply that a genetic basis is nonexistent, but does suggest that it is distinct from the polygenic risk score for schizophrenia.

Item Type: Article
Date Type: Publication
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Medicine
Systems Immunity Research Institute (SIURI)
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: R Medicine > R Medicine (General)
Additional Information: Nick Craddock, Valentina Escott-Price, Marian Hamshere, Peter Holmans, George Kirov, Michael O'Donovan, Michael Owen and Stanley Zammit are collaborators on this article.
Publisher: Public Library of Science
ISSN: 1932-6203
Date of First Compliant Deposit: 30 March 2016
Last Modified: 06 May 2023 12:14
URI: https://orca.cardiff.ac.uk/id/eprint/79809

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