The International Journal of Neuropsychopharmacology

Table of Contents - May 2011 - Volume 14, Issue 04 (Thematic Section: Consequences of Developmental Exposure to Drugs, Hormones or Altered Environment)  

Trends and Perspectives

Pathway-based analysis of GWAS datasets: effective but caution required

Peilin Jiaa1a2, Lily Wanga3, Herbert Y. Meltzera2 and Zhongming Zhaoa1a2a4 c1

a1 Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, TN, USA

a2 Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, TN, USA

a3 Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, TN, USA

a4 Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA

Abstract

Pathway-based analysis is rapidly emerging as an alternative but powerful approach for searching for disease causal genes from genomic datasets and has been applied to many complex diseases recently, but it is only now beginning to be applied in psychiatry. Here, we discuss critical issues in the pathway-based approach by specifically comparing the first pathway analysis of genome-wide association studies (GWAS) datasets in neuropsychiatric disorders by O'Dushlaine and colleagues (Molecular Psychiatry 2010, doi:10.1038/mp.2010.7) with our analysis. We also computed the power of gene set enrichment analysis, hypergeometric test, and SNP ratio test in order to assist future applications of these methods in pathway-based analysis of GWAS datasets. Overall, we suggest that the pathway-based approach is effective but caution is needed in interpreting the results of such analysis.

(Received April 30 2010)

(Reviewed August 07 2010)

(Revised October 10 2010)

(Accepted November 13 2010)

(Online publication December 16 2010)

Key Words:

Correspondence:

c1 Address for correspondence: Professor Z. Zhao, Department of Psychiatry, Vanderbilt University School of Medicine, 2525 West End Avenue, Suite 600, Nashville, TN 37203, USA. Tel.: (615) 343-9158 Fax: (615) 936-8545 Email: zhongming.zhao@vanderbilt.edu

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