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Prioritization and Evaluation of Depression Candidate Genes by Combining Multidimensional Data Resources

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  • Chung-Feng Kao
  • Yu-Sheng Fang
  • Zhongming Zhao
  • Po-Hsiu Kuo

Abstract

Background: Large scale and individual genetic studies have suggested numerous susceptible genes for depression in the past decade without conclusive results. There is a strong need to review and integrate multi-dimensional data for follow up validation. The present study aimed to apply prioritization procedures to build-up an evidence-based candidate genes dataset for depression. Methods: Depression candidate genes were collected in human and animal studies across various data resources. Each gene was scored according to its magnitude of evidence related to depression and was multiplied by a source-specific weight to form a combined score measure. All genes were evaluated through a prioritization system to obtain an optimal weight matrix to rank their relative importance with depression using the combined scores. The resulting candidate gene list for depression (DEPgenes) was further evaluated by a genome-wide association (GWA) dataset and microarray gene expression in human tissues. Results: A total of 5,055 candidate genes (4,850 genes from human and 387 genes from animal studies with 182 being overlapped) were included from seven data sources. Through the prioritization procedures, we identified 169 DEPgenes, which exhibited high chance to be associated with depression in GWA dataset (Wilcoxon rank-sum test, p = 0.00005). Additionally, the DEPgenes had a higher percentage to express in human brain or nerve related tissues than non-DEPgenes, supporting the neurotransmitter and neuroplasticity theories in depression. Conclusions: With comprehensive data collection and curation and an application of integrative approach, we successfully generated DEPgenes through an effective gene prioritization system. The prioritized DEPgenes are promising for future biological experiments or replication efforts to discoverthe underlying molecular mechanisms for depression.

Suggested Citation

  • Chung-Feng Kao & Yu-Sheng Fang & Zhongming Zhao & Po-Hsiu Kuo, 2011. "Prioritization and Evaluation of Depression Candidate Genes by Combining Multidimensional Data Resources," PLOS ONE, Public Library of Science, vol. 6(4), pages 1-9, April.
  • Handle: RePEc:plo:pone00:0018696
    DOI: 10.1371/journal.pone.0018696
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    References listed on IDEAS

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    1. Vaishnav Krishnan & Eric J. Nestler, 2008. "The molecular neurobiology of depression," Nature, Nature, vol. 455(7215), pages 894-902, October.
    2. Ekaterini Blaveri & Fiona Kelly & Alessandra Mallei & Kriss Harris & Adam Taylor & Juliet Reid & Maria Razzoli & Lucia Carboni & Chiara Piubelli & Laura Musazzi & Girogio Racagni & Aleksander Mathé & , 2010. "Expression Profiling of a Genetic Animal Model of Depression Reveals Novel Molecular Pathways Underlying Depressive-Like Behaviours," PLOS ONE, Public Library of Science, vol. 5(9), pages 1-10, September.
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