Specific glial functions contribute to schizophrenia susceptibility
Andrea Goudriaan1, Christiaan de Leeuw2, Stephan Ripke3
1Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Amsterdam, the Netherlands; danielle.posthuma@vu.nl.
Schizophrenia Bulletin
|August 20, 2013
Summary
Genetic links between glial cells and schizophrenia risk were found. Astrocytes and oligodendrocytes, but not microglia, are associated with increased schizophrenia susceptibility, highlighting glia
Area of Science:
- Neuroscience
- Genetics
- Psychiatry
Background:
- Schizophrenia is a complex brain disorder with a strong genetic component.
- The traditional focus for schizophrenia etiology has been neuronal dysfunction.
- Emerging evidence suggests glial cells are crucial for synaptic transmission and brain function.
Purpose of the Study:
- To investigate the causal involvement of the three main glial cell lineages in schizophrenia risk.
- To analyze the combined effects of genetic variants in glial type-specific genes on schizophrenia susceptibility.
Main Methods:
- Functional gene set analysis was performed.
- Genome-wide association data from a large schizophrenia cohort (13,689 cases, 18,226 controls) was utilized.
Main Results:
- Gene sets for astrocytes and oligodendrocytes were significantly associated with increased schizophrenia risk.
- Microglia gene sets did not show a significant association with schizophrenia risk.
- Astrocyte and oligodendrocyte associations relate to synaptic signaling, myelin integrity, glial development, and epigenetic regulation.
Conclusions:
- Genetic factors influencing astrocyte and oligodendrocyte function contribute to schizophrenia susceptibility.
- The findings support extending the neuronal hypothesis of schizophrenia to include the critical role of glial cells.
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