Integrative mouse and human mRNA studies using WGCNA nominates novel candidate genes involved in the pathogenesis of major depressive disorder

Karim Malki*, Maria Grazia Tosto, Irfan Jumabhoy, Anbarasu Lourdusamy, Frans Sluyter, Ian Craig, Rudolf Uher, Peter McGuffin, Leonard C. Schalkwyk

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)

Abstract

Aim: This study aims to identify novel genes associated with major depressive disorder and pharmacological treatment response using animal and human mRNA studies. Materials & methods: Weighted gene coexpression network analysis was used to uncover genes associated with stress factors in mice and to inform mRNA probe set selection in a post-mortem study of depression. Results: A total of 171 genes were found to be differentially regulated in response to both early and late stress protocols in a mouse study. Ten human genes, orthologous to mouse genes differentially expressed by stress, were also found to be dysregulated in depressed cases in a human post-mortem brain study from the Stanley Foundation Brain Collection. Conclusion: Several novel genes associated with depression were uncovered, including NOVA1 and USP9X. Moreover, we found further evidence in support of hippocampal neurogenesis and peripheral inflammation in major depressive disorder.

Original languageEnglish
Pages (from-to)1979-1990
Number of pages12
JournalPHARMACOGENOMICS
Volume14
Issue number16
DOIs
Publication statusPublished - Dec 2013

Keywords

  • depression
  • escitalopram
  • GENDEP
  • nortriptyline
  • pharmacogenetics
  • GENOME-WIDE ASSOCIATION
  • COEXPRESSION NETWORK ANALYSIS
  • FACTOR-KAPPA-B
  • ANTIDEPRESSANT RESPONSE
  • POSTMORTEM BRAINS
  • CLINICAL-PRACTICE
  • MENTAL-DISORDERS
  • BIPOLAR DISORDER
  • ANIMAL-MODELS
  • METAANALYSIS
  • Acknowledged-BRC
  • Acknowledged-BRC-13/14

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