Schizophrenia Research
Volume 122, Issue 1 , Pages 38-42, September 2010

Common variants conferring risk of schizophrenia: A pathway analysis of GWAS data

  • Peilin Jia

      Affiliations

    • Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    • Department of Psychiatry, Vanderbilt University, Nashville, TN 37232, USA
    • ,
  • Lily Wang

      Affiliations

    • Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    • ,
  • Herbert Y. Meltzer

      Affiliations

    • Department of Psychiatry, Vanderbilt University, Nashville, TN 37232, USA
    • ,
  • Zhongming Zhao

      Affiliations

    • Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    • Department of Psychiatry, Vanderbilt University, Nashville, TN 37232, USA
    • Corresponding Author InformationCorresponding author. Department of Biomedical Informatics, Vanderbilt University School of Medicine, 2525 West End Avenue, Suite 600, Nashville, TN 37203, USA. Tel.: +1 615 343 9158; fax: +1 615 936 8545.

Received 18 April 2010; received in revised form 26 June 2010; accepted 1 July 2010. published online 26 July 2010.

Abstract 

Unlike the typical analysis of single markers in genome-wide association studies (GWAS), we incorporated Gene Set Enrichment Analysis (GSEA) and hypergeometric test and combined them using Fisher's combined method to perform pathway-based analysis in order to detect genes' combined effects on mediating schizophrenia. A few pathways were consistently found to be top ranked and likely associated with schizophrenia by these methods; they are related to metabolism of glutamate, the process of apoptosis, inflammation, and immune system (e.g., glutamate metabolism pathway, TGF-beta signaling pathway, and TNFR1 pathway). The genes involved in these pathways had not been detected by single marker analysis, suggesting this approach may complement the original analysis of GWAS dataset.

Keywords: Schizophrenia, Gene set enrichment analysis, GWAS, Pathway, Candidate gene

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PII: S0920-9964(10)01380-0

doi:10.1016/j.schres.2010.07.001

Schizophrenia Research
Volume 122, Issue 1 , Pages 38-42, September 2010

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