Fibroblast and lymphoblast gene expression profiles in schizophrenia: are non-neural cells informative? Author

نویسندگان

  • D. McCurdy
  • Nicholas A. Matigian
  • Richard D. McCurdy
  • François Féron
  • Christopher Perry
  • Heather Smith
  • Cheryl Filippich
  • Duncan McLean
  • John McGrath
  • Alan Mackay-Sim
  • Bryan Mowry
  • Nicholas K. Hayward
چکیده

Lymphoblastoid cell lines (LCLs) and fibroblasts provide conveniently derived non-neuronal samples in which to investigate the aetiology of schizophrenia (SZ) using gene expression profiling. This assumes that heritable mechanisms associated with risk of SZ have systemic effects and result in changes to gene expression in all tissues. The broad aim of this and other similar studies is that comparison of the transcriptomes of non-neuronal tissues from SZ patients and healthy controls may identify gene/pathway dysregulation underpinning the neurobiological defects associated with SZ. Using microarrays consisting of 18,664 probes we compared gene expression profiles of LCLs from SZ cases and healthy controls. To identify robust associations with SZ that were not patient or tissue specific, we also examined fibroblasts from an independent series of SZ cases and controls using the same microarrays. In both tissue types ANOVA analysis returned approximately the number of differentially expressed genes expected by chance. No genes were significantly differentially expressed in either tissue when corrected for multiple testing. Even using relaxed parameters (p#0.05, without multiple testing correction) there were still no differentially expressed genes that also displayed $2-fold change between the groups of SZ cases and controls common to both LCLs and fibroblasts. We conclude that despite encouraging data from previous microarray studies assessing non-neural tissues, the lack of a convergent set of differentially expressed genes associated with SZ using fibroblasts and LCLs indicates the utility of non-neuronal tissues for detection of gene expression differences and/or pathways associated with SZ remains to be demonstrated. Citation: Matigian NA, McCurdy RD, Féron F, Perry C, Smith H, et al. (2008) Fibroblast and Lymphoblast Gene Expression Profiles in Schizophrenia: Are Non-Neural Cells Informative?. PLoS ONE 3(6): e2412. doi:10.1371/journal.pone.0002412 Editor: Bernhard Baune, James Cook University, Australia Received March 13, 2008; Accepted April 27, 2008; Published June 11, 2008 Copyright: 2008 Matigian et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by grants from the Ipswich Hospital Foundation and the Garnett Passe and Rodney Williams Memorial Foundation. Neither agency had any further role in study design, analysis and interpretation of data, writing of the report or decision to submit the manuscript for publication. Competing Interests: The authors have declared that no competing interests exist. * E-mail: [email protected]

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Fibroblast and Lymphoblast Gene Expression Profiles in Schizophrenia: Are Non-Neural Cells Informative?

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تاریخ انتشار 2017