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

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, diso...

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Main Authors: Eske M Derks, Jacob A S Vorstman, Stephan Ripke, Rene S Kahn, Schizophrenia Psychiatric Genomic Consortium, Roel A Ophoff
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0037852&type=printable
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author Eske M Derks
Jacob A S Vorstman
Stephan Ripke
Rene S Kahn
Schizophrenia Psychiatric Genomic Consortium
Roel A Ophoff
author_facet Eske M Derks
Jacob A S Vorstman
Stephan Ripke
Rene S Kahn
Schizophrenia Psychiatric Genomic Consortium
Roel A Ophoff
author_sort Eske M Derks
collection DOAJ
description 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.
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spelling doaj-art-8e803611ef2a448791142017a44705d12025-08-20T03:25:11ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0176e3785210.1371/journal.pone.0037852Investigation of the genetic association between quantitative measures of psychosis and schizophrenia: a polygenic risk score analysis.Eske M DerksJacob A S VorstmanStephan RipkeRene S KahnSchizophrenia Psychiatric Genomic ConsortiumRoel A OphoffThe 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0037852&type=printable
spellingShingle Eske M Derks
Jacob A S Vorstman
Stephan Ripke
Rene S Kahn
Schizophrenia Psychiatric Genomic Consortium
Roel A Ophoff
Investigation of the genetic association between quantitative measures of psychosis and schizophrenia: a polygenic risk score analysis.
PLoS ONE
title Investigation of the genetic association between quantitative measures of psychosis and schizophrenia: a polygenic risk score analysis.
title_full Investigation of the genetic association between quantitative measures of psychosis and schizophrenia: a polygenic risk score analysis.
title_fullStr Investigation of the genetic association between quantitative measures of psychosis and schizophrenia: a polygenic risk score analysis.
title_full_unstemmed Investigation of the genetic association between quantitative measures of psychosis and schizophrenia: a polygenic risk score analysis.
title_short Investigation of the genetic association between quantitative measures of psychosis and schizophrenia: a polygenic risk score analysis.
title_sort investigation of the genetic association between quantitative measures of psychosis and schizophrenia a polygenic risk score analysis
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0037852&type=printable
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