The emerging molecular architecture of schizophrenia, polygenic risk scores and the clinical implications for GxE research

Conrad Iyegbe*, Desmond Campbell, Amy Butler, Olesya Ajnakina, Pak Sham

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

64 Citations (Scopus)

Abstract

Schizophrenia is a devastating mental disorder. The level of risk in the general population is sustained by the persistence of social, environmental and biological factors, as well as their interactions. Socio-environmental risk factors for schizophrenia are well established and robust. The same can belatedly be said of genetic risk factors for the disorder. Recent progress in schizophrenia genetics is primarily fuelled by genome-wide association, which is able to leverage substantial proportions of additional explained variance previously classified as 'missing'. Here, we provide an outline of the emerging genetic landscape of schizophrenia and demonstrate how this knowledge can be turned into a simple empirical measure of genetic risk, known as a polygenic risk score. We highlight the statistical framework used to assess the clinical potential of the new score and finally, draw relevance to and discuss the clinical implications for the study of gene-environment interaction.

Original languageEnglish
Pages (from-to)169-182
Number of pages14
JournalSocial Psychiatry and Psychiatric Epidemiology
Volume49
Issue number2
DOIs
Publication statusPublished - 1 Feb 2014

Keywords

  • Gene-environment interaction
  • GWAS
  • GWEIS
  • Polygenic risk score
  • Prediction
  • Schizophrenia

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