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Schizophrenia Beyond Genome-Wide Association Studies: It's About Time
Giulio Pergola1,2,3,4, Daniel R Weinberger1,2,3,5,6
1Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore.
The American Journal of Psychiatry
|August 1, 2026
Summary
Schizophrenia risk involves complex gene and environmental interactions that change over time. Studying these dynamic patterns offers new avenues for personalized treatments and prevention strategies.
Area of Science:
- Neuroscience
- Genetics
- Systems Biology
Background:
- Hundreds of schizophrenia risk genes identified, yet individual disease mechanisms remain unclear.
- Gene functions implicated in schizophrenia are diverse, suggesting convergent biological pathways.
- Gene coexpression patterns may represent systems-level risk mediation.
Purpose of the Study:
- To explore the dynamic interplay between gene coexpression patterns, environmental exposures, and schizophrenia risk over development.
- To investigate how shifting coexpression patterns influence the variable expressivity of genetic risk.
- To propose a framework for studying molecular and behavioral patterns over time for novel treatment development.
Main Methods:
- Analysis of gene coexpression patterns across developmental stages.
- Integration of environmental exposure data with genetic risk factors.
- Longitudinal study of molecular and behavioral patterns.
Main Results:
- Gene coexpression related to schizophrenia risk is dynamic, changing in importance over time.
- Both systems biology of risk and environmental exposures are time-dependent.
- Dynamic gene-environment interplay, driven by shifting coexpression, may explain variable genetic risk expressivity.
Conclusions:
- The dynamic interplay between shifting gene coexpression patterns and environmental exposures is crucial for understanding schizophrenia's variable expressivity.
- Gene-environment correlations can influence individual experiences and life events, impacting disease trajectory.
- Paired longitudinal study of molecular and behavioral patterns is essential for developing targeted treatments and preventive strategies for schizophrenia.
Keywords:
Brain DevelopmentGene Co-expression NetworksGene-Environment InterplayPolygenic Risk ScoreSchizophreniaSystems BiologyMore Related Videos
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