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Comparative Study
. 2012;7(6):e37852.
doi: 10.1371/journal.pone.0037852. Epub 2012 Jun 22.

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

Eske M Derks  1 , Jacob A S Vorstman, Stephan Ripke, Rene S Kahn; Schizophrenia Psychiatric Genomic Consortium; Roel A Ophoff
Collaborators, Affiliations
Comparative Study

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

Eske M Derks et al. PLoS One. 2012.

Erratum in

  • PLoS One. 2013;8(3). doi:10.1371/annotation/6ff0353a-cc91-4d12-896a-d1de0dcb0fe0

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.

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Conflict of interest statement

Competing Interests: The authors declare the following interests: Eli Lilly funded portions of the genotyping for CATIE and TOP. P.F.S. received research funding from Eli Lilly in connection with CATIE. T.S.S. received research funding from Eli Lilly and consulting fees from Janssen Pharmaceutica, GlaxoSmithKline and Bristol-Myers Squibb. J.A.L. received research funding from AstraZeneca Pharmaceuticals, Bristol-Myers Squibb, GlaxoSmithKline, Janssen Pharmaceutica and Pfizer and consulting and educational fees from AstraZeneca Pharmaceuticals, Bristol-Myers Squibb, Eli Lilly, Forest Pharmaceuticals, GlaxoSmithKline, Janssen Pharmaceutica, Novartis, Pfizer and Solvay. D.St.C. received research funding from GlaxoSmithKline and Generation Scotland, Genetics Health Initiative. F.A. received funds from Pfizer, Organon and the Foundation for the National Institutes of Health. D.W.B. has received research support from Shire and Forest, has been on the speakers' bureau for Pfizer and has received consulting honoraria from Forest and Jazz. T.W. has received consulting and lecture fees from H. Lundbeck A/S. O.A.A. has received Speaker's honorarium from AstraZeneca, Janssen, Bristol-Myers Squibb and GlaxoSmithKline. I.M. has received a Speaker's honorarium from Janssen and AstraZeneca. A.K.M. has received consulting fees or honoraria from Eli Lilly & Company, Janssen Pharmaceutica, Merck, Bristol-Meyers Squibb, Pfizer, PGxHealth (a division of Clinical Data, Inc.), Roche Diagnostics and Vanda Pharmaceuticals and has received research support from Eli Lilly & Company. T.L. has received consulting fees or honoraria from Merck, Eli Lilly & Company, Golden Helix, Inc., InforMed Insights and PGxHealth (a division of Clinical Data, Inc.). I.B. has been an advisory board member, consultant and lecturer for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, EGIS, Janssen, H. Lundbeck A/S, Novartis, Pfizer, Richter and Schering-Plough and received a grant for an investigator-initiated study from H. Lundbeck A/S. J.J.M. has received consulting and speaker's fees from Johnson & Johnson, Schering-Plough and Eli Lilly. C.P. has received grant support from Janssen-Cilag, Eli Lilly, Hospira (Mayne) and AstraZeneca, provided consultancy to Janssen-Cilag, Eli Lilly, Hospira (Mayne), AstraZeneca, Pfizer and Schering-Plough and has undertaken investigator-initiated studies supported by Eli Lilly, Hospira, Janssen Cilag and AstraZeneca. The Denmark-Aarhus group (The GEMS Stud with principal investigators A.D.B., O.M. and P.B.M.) received research funding from H. Lundbeck A/S. E.G.J. has served as an unpaid consultant for Eli Lilly. H.S., S.S., and K.S. are employed at deCODE Genetics, Reykjavik, Iceland. MH is employed at Illumina, Inc., La Jolla, California, USA. PM is employed at NeuroSearch A/S, Ballerup, Denmark. TFO is employed at ARoS Applied Biotechnology A/S, Skejby, Denmark. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials, as detailed online in the guide for authors.

Figures

Figure 1a–e
Figure 1a–e. e. Associations between symptom dimension scores and genetic risk scores.
Legend “The red dots represent cases and the blue dots represent controls. The regression lines represent the association between genetic risk score and dimension scores in the total sample (black) in cases (red) and in controls (blue).
See this image and copyright information in PMC

References

    1. van Os J, Kapur S. Schizophrenia. Lancet. 2009;374:635–645. - PubMed
    1. van Os J, Hanssen M, Bijl RV, Ravelli A. Strauss (1969) revisited: a psychosis continuum in the general population? Schizophr Res. 2000;45:11–20. - PubMed
    1. van Os J, Linscott RJ, Myin-Germeys I, Delespaul P, Krabbendam L. A systematic review and meta-analysis of the psychosis continuum: evidence for a psychosis proneness-persistence-impairment model of psychotic disorder. Psychol Med. 2009;39:179–195. - PubMed
    1. Binbay T, Drukker M, Elbi H, Aksu TF, Ozkinay F, et al. (in press) Testing the Psychosis Continuum: Differential Impact of Genetic and Nongenetic Risk Factors and Comorbid Psychopathology Across the Entire Spectrum of Psychosis. Schizophr Bull. - PMC - PubMed
    1. Plomin R, Owen MJ, McGuffin P, et al. The genetic basis of complex human behaviors. Science. 1994;264:1733–1739. - PubMed

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