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Network analysis of positional candidate genes of schizophrenia highlights myelin-related pathways

Molecular Psychiatry volume 14, pages 353–355 (2009)Cite this article

Meta-analyses of linkage studies in schizophrenia have identified genomic regions that most plausibly harbor genes underlying the disorder.1, 2 Although the idea that the actions of these susceptibility genes for schizophrenia may converge in common biological pathways is well supported, little is known about the molecular relationship between the positional candidate genes for schizophrenia. We hypothesized that by analyzing functional interactions of these positional candidate genes, biological pathways involved in the etiology of schizophrenia may be revealed.

Here we present an analysis using gene expression data of positional candidate genes of schizophrenia and identify modules of co-expressed genes that are likely to be functionally related. For this purpose we used a publicly available gene-expression data set3 containing data on 19 648 autosomal transcripts collected from peripheral blood lymphocytes of 304 unrelated healthy individuals. We selected the transcripts of genes under the schizophrenia linkage peaks as identified by two well-established meta-analyses.1, 2 We subsequently selected those transcripts that are expressed in human brain-tissue according to the National Center for Biotechnology Information UniGene database (build 36.3). Lastly, we selected only transcripts with a substantial heritability estimate (>0.3) as estimated by Göring et al.3 This threshold was used as quality measure for the observed transcription levels (HH Göring, personal communication). Moreover, transcripts for which the variation of gene expression is to a large degree explained by genetic variation may be stronger candidates for disease susceptibility. Using these criteria, we winnowed down the set of positional candidate genes for schizophrenia from 1602 to a final list of 766 transcripts corresponding to 13 linkage regions on 11 chromosomes. The transcripts are listed in Supplementary Table 1, together with their genetic location, heritability estimates and brain-tissue expression levels.

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Authors and Affiliations

  1. Department of psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, Utrecht, The Netherlands

    T Rietkerk, M P M Boks, I E C Sommer & R S Kahn

  2. Complex Genetics Section, DBG-Dept Medical Genetics and The Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands

    S de Jong & R A Ophoff

  3. Center for Neurobehavioral Genetics, University of Calfornia, Los Angeles, California, USA

    R A Ophoff

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  1. T Rietkerk
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  2. M P M Boks
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  3. I E C Sommer
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  4. S de Jong
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  5. R S Kahn
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  6. R A Ophoff
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Corresponding author

Correspondence to T Rietkerk.

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Supplementary Information accompanies the paper on the Molecular Psychiatry website (http://www.nature.com/mp)

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Rietkerk, T., Boks, M., Sommer, I. et al. Network analysis of positional candidate genes of schizophrenia highlights myelin-related pathways. Mol Psychiatry 14, 353–355 (2009). https://doi.org/10.1038/mp.2008.86

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