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

Ruud van Winkel*, Gabriel Esquivel, Gunter Kenis, Marieke Wichers, Dina Collip, Odette Peerbooms, Bart Rutten, Inez Myin-Germeys, Jim van Os

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

68 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)e185-e192
Number of pages8
JournalCNS Neuroscience & Therapeutics
Volume16
Issue number5
DOIs
Publication statusPublished - 2010
Externally publishedYes

Keywords

  • Cannabis
  • Gene-environment interaction
  • GWAS
  • Psychosis
  • Trauma
  • DAILY-LIFE STRESS
  • VAL(158)MET MODERATION
  • DOPAMINE RELEASE
  • COMMON VARIANTS
  • CANDIDATE GENES
  • HUMAN STRIATUM
  • PSYCHOSIS
  • ASSOCIATION
  • CANNABIS
  • DELETIONS

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