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An association screen of myelin-related genes implicates the chromosome 22q11 PIK4CA gene in schizophrenia

Molecular Psychiatry volume 13, pages 1060–1068 (2008)Cite this article

Abstract

Several lines of evidence, including expression analyses, brain imaging and genetic studies suggest that the integrity of myelin is disturbed in schizophrenia patients. In this study, we first reconstructed a pathway of 138 myelin-related genes, all involved in myelin structure, composition, development or maintenance. Then we performed a two-stage association analysis on these 138 genes using 771 single nucleotide polymorphisms (SNPs). Analysis of our data from 310 cases vs 880 controls demonstrated association of 10 SNPs from six genes. Specifically, we observed highly significant P-values for association in PIK4CA (observed P=6.1 × 10−6). These findings remained significant after Bonferroni correction for 771 tests. The PIK4CA gene is located in the chromosome 22q11 deletion syndrome region, which is of particular interest because it has been implicated in schizophrenia. We also report weak association of SNPs in PIK3C2G, FGF1, FGFR1, ARHGEF10 and PSAP (observed P⩽0.01). Our approach—of screening genes involved in a particular pathway for association—resulted in identification of several, mostly novel, genes associated with the risk of developing schizophrenia in the Dutch population.

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Acknowledgements

We thank all the patients for their participation in this study and Jackie Senior for critically reading the manuscript. This study was financially supported by the Makaria Foundation and the Dutch Brain Foundation (Hersenstichting).

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Author notes

  1. B J Jungerius and M L C Hoogendoorn: These authors contributed equally to this study.

Authors and Affiliations

  1. DBG-Department of Medical Genetics, Complex Genetics Section, University Medical Center Utrecht, Utrecht, The Netherlands

    B J Jungerius, S C Bakker, R van't Slot, A F Bardoel, R A Ophoff, C Wijmenga & R J Sinke

  2. Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands

    M L C Hoogendoorn, S C Bakker & R S Kahn

  3. Rudolf Magnus Institute, University Medical Center Utrecht, Utrecht, The Netherlands

    R A Ophoff

  4. Department of Human Genetics and Center for Neurobehavioral Genetics, UCLA, Los Angeles, CA, USA

    R A Ophoff

  5. Department of Human Genetics, University Medical Center Groningen, Groningen, The Netherlands

    C Wijmenga

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Correspondence to R J Sinke.

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

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Jungerius, B., Hoogendoorn, M., Bakker, S. et al. An association screen of myelin-related genes implicates the chromosome 22q11 PIK4CA gene in schizophrenia. Mol Psychiatry 13, 1060–1068 (2008). https://doi.org/10.1038/sj.mp.4002080

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