Document Detail


Risk architecture of schizophrenia: the role of epigenetics.
MedLine Citation:
PMID:  23318661     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE OF REVIEW: To systematize existing data and review new findings on the cause of schizophrenia and outline an improved mixed model of schizophrenia risk.
RECENT FINDINGS: Multiple and variable genetic and environmental factors interact to influence the risk of schizophrenia. Both rare variants with large effect and common variants with small effect contribute to genetic risk of schizophrenia, with no indication for differential impact on its clinical features. Accumulating evidence supports a genetic architecture of schizophrenia with multiple scenarios, including additive polygenic, heterogeneity, and mixed polygenic-heterogeneity. The epigenetic mechanisms that mediate gene-environment (GxE) interactions provide a framework to incorporate environmental factors into models of schizophrenia risk. Environmental pathogens with small effect on risk have robust effects in the context of family history of schizophrenia. Hence, genetic risk for schizophrenia may be expressed in part as sensitivity to environmental factors.
SUMMARY: We propose an improved mixed model of schizophrenia risk in which abnormal epigenetic states with large effects are superimposed on a polygenic liability to schizophrenia. This scenario can account for GxE interactions and shared family environment, which in many cases are not explained by a single structural variant of large effect superimposed on polygenes (the traditional mixed model).
Authors:
Dragan M Svrakic; Charles F Zorumski; Nenad M Svrakic; Igor Zwir; Claude R Cloninger
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Review    
Journal Detail:
Title:  Current opinion in psychiatry     Volume:  26     ISSN:  1473-6578     ISO Abbreviation:  Curr Opin Psychiatry     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-01-31     Completed Date:  2013-07-09     Revised Date:  2014-06-17    
Medline Journal Info:
Nlm Unique ID:  8809880     Medline TA:  Curr Opin Psychiatry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  188-95     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Epigenesis, Genetic*
Gene-Environment Interaction*
Humans
Risk Factors
Schizophrenia / genetics*
Grant Support
ID/Acronym/Agency:
MH077791/MH/NIMH NIH HHS; R01 MH077791/MH/NIMH NIH HHS

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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