REVIEW: Genome-Wide Findings in Schizophrenia and the Role of Gene–Environment Interplay

Authors

  • Ruud Van Winkel,

    1. Department of Psychiatry and Neuropsychology, EURON, South Limburg Mental Health Research and Teaching Network, Maastricht University Medical Centre, MD Maastricht, The Netherlands
    2. University Psychiatric Centre, Catholic University Leuven, Kortenberg, Belgium
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  • Gabriel Esquivel,

    1. Department of Psychiatry and Neuropsychology, EURON, South Limburg Mental Health Research and Teaching Network, Maastricht University Medical Centre, MD Maastricht, The Netherlands
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  • Gunter Kenis,

    1. Department of Psychiatry and Neuropsychology, EURON, South Limburg Mental Health Research and Teaching Network, Maastricht University Medical Centre, MD Maastricht, The Netherlands
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  • Marieke Wichers,

    1. Department of Psychiatry and Neuropsychology, EURON, South Limburg Mental Health Research and Teaching Network, Maastricht University Medical Centre, MD Maastricht, The Netherlands
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  • Dina Collip,

    1. Department of Psychiatry and Neuropsychology, EURON, South Limburg Mental Health Research and Teaching Network, Maastricht University Medical Centre, MD Maastricht, The Netherlands
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  • Odette Peerbooms,

    1. Department of Psychiatry and Neuropsychology, EURON, South Limburg Mental Health Research and Teaching Network, Maastricht University Medical Centre, MD Maastricht, The Netherlands
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  • Bart Rutten,

    1. Department of Psychiatry and Neuropsychology, EURON, South Limburg Mental Health Research and Teaching Network, Maastricht University Medical Centre, MD Maastricht, The Netherlands
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  • Inez Myin-Germeys,

    1. Department of Psychiatry and Neuropsychology, EURON, South Limburg Mental Health Research and Teaching Network, Maastricht University Medical Centre, MD Maastricht, The Netherlands
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  • Jim Van Os

    1. Department of Psychiatry and Neuropsychology, EURON, South Limburg Mental Health Research and Teaching Network, Maastricht University Medical Centre, MD Maastricht, The Netherlands
    2. Division of Psychological Medicine, Institute of Psychiatry, London, UK
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Correspondence
Dr. Ruud van Winkel, M.D., Ph.D., School of Mental Health and Neuroscience (MheNS), Maastricht University Medical Centre, Vijverdalseweg 1, Concorde Building (SN2), 6200 MD Maastricht, The Netherlands.
Tel.: +31-43-36-85-372;
Fax: +31-43-36-88-689;
E-mail: ruud.vanwinkel@sp.unimaas.nl

Abstract

The recent advent of genome-wide mass-marker technology has resulted in renewed optimism to unravel the genetic architecture of psychotic disorders. Genome-wide association studies have identified a number of common polymorphisms robustly associated with schizophrenia, in ZNF804A, transcription factor 4, major histocompatibility complex, and neurogranin. In addition, copy number variants (CNVs) in 1q21.1, 2p16.3, 15q11.2, 15q13.3, 16p11.2, and 22q11.2 were convincingly implicated in schizophrenia risk. Furthermore, these studies have suggested considerable genetic overlap with bipolar disorder (particularly for common polymorphisms) and neurodevelopmental disorders such as autism (particularly for CNVs). The influence of these risk variants on relevant intermediate phenotypes needs further study. In addition, there is a need for etiological models of psychosis integrating genetic risk with environmental factors associated with the disorder, focusing specifically on environmental impact on gene expression (epigenetics) and convergence of genes and environment on common biological pathways bringing about larger effects than those of genes or environment in isolation (gene–environment interaction). Collaborative efforts that bring together expertise in statistics, genetics, epidemiology, experimental psychiatry, brain imaging, and clinical psychiatry will be required to succeed in this challenging task.

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