Andrea Goudriaan et al publish in Schizophrenia Bulletin

10 September 2013

Andrea Goudriaan and colleagues show that sets of genes involved in specific glial function are associated with the risk to develop schizophrenia. They used genomewide association (GWA) data from 13,689 schizophrenic patients and 18,226 controls from the Psychiatric Genomics Consortium and the Swedish Schizophrenia sample.

Schizophrenia is a highly polygenic disorder. It is likely influenced by thousands of genetic variants, each of small effect. “Detecting these small effects is difficult and therefore gene-set analyses – in which the combined effect of multiple genetic variants is evaluated – has been proposed as a promising tool in elucidating the underlying biology of polygenic disorders‚, explains CNCR PhD student Christiaan de Leeuw. De Leeuw conducted the statistical analyses for the study.

More than a year
A crucial step in gene-set analyses is to define the gene-sets. Goudriaan devoted over a year of her PhD time to carefully construct sets of genes that have similar cellular function. “We focused on genes involved in glial function, as aberrant glial function has been implicated in schizophrenia previously. I carefully annotated over 4000 genes and categorized them into 79 sets of functionally related genes that are overrepresented in either astrocytes, oligodendrocytes or microglia‚, Goudriaan adds.

Gene-set analysis revealed significant associations between six gene-sets involved in specific astrocytic function and three gene-sets involved in oligodendrocytic function. Microglia function was not associated with schizophrenia. The astrocyte findings are in line with the implication of neuron-glia tripartite communication in schizophrenia, and warrant further experimental investigation on the mechanisms underlying the glial contribution to schizophrenia.

“Our results indicate that glial cells are key candidates contributing to the primary development of underlying pathological processes of schizophrenia, which may have important implications for its understanding and treatment. Furthermore, these results encourage to use our glial gene-set list for investigating the involvement of glial cells in other polygenic brain disorders‚, remarks Goudriaan.


The study was published online August 16, 2013 in Schizophrenia Bulletin:

Andrea Goudriaan, Christiaan de Leeuw, Stephan Ripke, Christina M. Hultman, Pamela Sklar, Patrick F. Sullivan, August B. Smit, Danielle Posthuma, and Mark H. G. Verheijen. Specific Glial Functions Contribute to Schizophrenia Susceptibility.

Schizophr Bull first published online August 16, 2013