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Functional gene group analysis identifies synaptic gene groups as risk factor for schizophrenia.
E S Lips1, L N Cornelisse, R F Toonen
1Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, Amsterdam, The Netherlands.
Molecular Psychiatry
|September 21, 2011
Summary
Genetic analysis reveals that synaptic gene groups are strongly associated with schizophrenia risk. This finding highlights the role of synaptic dysfunction in the disorder and may identify new drug targets.
Area of Science:
- Neuroscience
- Genetics
- Psychiatry
Background:
- Schizophrenia is a complex psychiatric disorder with high heritability.
- Previous research suggests synaptic dysfunction may contribute to schizophrenia's pathology.
Purpose of the Study:
- To investigate the association of genetic variants within synaptic gene groups with schizophrenia risk.
- To identify specific synaptic pathways involved in schizophrenia.
Main Methods:
- Functional gene group analysis was performed on a large cohort (4673 cases, 4965 controls).
- Accumulated genetic associations of expert-curated synaptic gene groups were tested against schizophrenia.
- Comparison with randomly drawn control gene groups assessed the significance of findings.
Main Results:
- A significant association was found between a group of 1026 synaptic genes and schizophrenia risk (P=7.6 × 10(-11)).
- This association was stronger than with random gene groups.
- Key contributing synaptic subgroups included intracellular signal transduction, excitability, and cell adhesion/trans-synaptic signaling.
Conclusions:
- The findings support the hypothesis of synaptic dysfunction in schizophrenia.
- Impaired intracellular signal transduction, synaptic excitability, and cell adhesion/trans-synaptic signaling are implicated in schizophrenia.
- Identifying affected gene groups may offer novel therapeutic targets.
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