Functional gene group analysis identifies synaptic gene groups as risk factor for schizophrenia

128Citations
Citations of this article
198Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Schizophrenia is a highly heritable disorder with a polygenic pattern of inheritance and a population prevalence of 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 (P7.6 × 10 11) and more strongly associated than 100 randomly drawn, matched control groups of genetic variants (P0.01). Subsequent analysis of synaptic subgroups suggested that the strongest association signals are derived from three synaptic gene groups: intracellular signal transduction (P2.0 × 10 4), excitability (P9.0 × 10 4) and cell adhesion and trans-synaptic signaling (P2.4 × 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. © 2012 Macmillan Publishers Limited All rights reserved.

Cite

CITATION STYLE

APA

Lips, E. S., Cornelisse, L. N., Toonen, R. F., Min, J. L., Hultman, C. M., Holmans, P. A., … Posthuma, D. (2012). Functional gene group analysis identifies synaptic gene groups as risk factor for schizophrenia. Molecular Psychiatry, 17(10), 996–1006. https://doi.org/10.1038/mp.2011.117

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free