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Functional gene group analysis identifies synaptic gene groups as risk factor for schizophrenia
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2012 (English)In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 17, no 10, 996-1006 p.Article in journal (Refereed) Published
Abstract [en]

Schizophrenia is a highly heritable disorder with a polygenic pattern of inheritance and a population prevalence of similar to 1%. Previous studies have implicated synaptic dysfunction in schizophrenia. We tested the accumulated association of genetic variants in expert-curated synaptic gene groups with schizophrenia in 4673 cases and 4965 healthy controls, using functional gene group analysis. Identifying groups of genes with similar cellular function rather than genes in isolation may have clinical implications for finding additional drug targets. We found that a group of 1026 synaptic genes was significantly associated with the risk of schizophrenia (P = 7.6 x 10(-11)) and more strongly associated than 100 randomly drawn, matched control groups of genetic variants (P < 0.01). Subsequent analysis of synaptic subgroups suggested that the strongest association signals are derived from three synaptic gene groups: intracellular signal transduction (P = 2.0 x 10(-4)), excitability (P = 9.0 x 10(-4)) and cell adhesion and trans-synaptic signaling (P = 2.4 x 10(-3)). These results are consistent with a role of synaptic dysfunction in schizophrenia and imply that impaired intracellular signal transduction in synapses, synaptic excitability and cell adhesion and trans-synaptic signaling play a role in the pathology of schizophrenia. Molecular Psychiatry (2012) 17, 996-1006; doi:10.1038/mp.2011.117; published online 20 September 2011

Place, publisher, year, edition, pages
2012. Vol. 17, no 10, 996-1006 p.
Keyword [en]
GWAS, ISC, GAIN, gene group analysis, synapse, genome-wide association
National Category
Clinical Medicine
URN: urn:nbn:se:uu:diva-184463DOI: 10.1038/mp.2011.117ISI: 000309214500005OAI: oai:DiVA.org:uu-184463DiVA: diva2:566632
Available from: 2012-11-09 Created: 2012-11-07 Last updated: 2012-11-09Bibliographically approved

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Psychiatry, Ulleråker, University Hospital
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