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

doi:10.2217/PGS.13.154

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 journal › Article › peer-review

51 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 language	English
Pages (from-to)	1979-1990
Number of pages	12
Journal	PHARMACOGENOMICS
Volume	14
Issue number	16
DOIs	https://doi.org/10.2217/PGS.13.154
Publication status	Published - 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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10.2217/PGS.13.154

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@article{178a6b5065484d7286881b27c47d9618,

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

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.",

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",

author = "Karim Malki and Tosto, {Maria Grazia} and Irfan Jumabhoy and Anbarasu Lourdusamy and Frans Sluyter and Ian Craig and Rudolf Uher and Peter McGuffin and Schalkwyk, {Leonard C.}",

year = "2013",

month = dec,

doi = "10.2217/PGS.13.154",

language = "English",

volume = "14",

pages = "1979--1990",

journal = "PHARMACOGENOMICS",

issn = "1462-2416",

publisher = "Future Medicine Ltd.",

number = "16",

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TY - JOUR

T1 - Integrative mouse and human mRNA studies using WGCNA nominates novel candidate genes involved in the pathogenesis of major depressive disorder

AU - Malki, Karim

AU - Tosto, Maria Grazia

AU - Jumabhoy, Irfan

AU - Lourdusamy, Anbarasu

AU - Sluyter, Frans

AU - Craig, Ian

AU - Uher, Rudolf

AU - McGuffin, Peter

AU - Schalkwyk, Leonard C.

PY - 2013/12

Y1 - 2013/12

N2 - 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.

AB - 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.

KW - depression

KW - escitalopram

KW - GENDEP

KW - nortriptyline

KW - pharmacogenetics

KW - GENOME-WIDE ASSOCIATION

KW - COEXPRESSION NETWORK ANALYSIS

KW - FACTOR-KAPPA-B

KW - ANTIDEPRESSANT RESPONSE

KW - POSTMORTEM BRAINS

KW - CLINICAL-PRACTICE

KW - MENTAL-DISORDERS

KW - BIPOLAR DISORDER

KW - ANIMAL-MODELS

KW - METAANALYSIS

KW - Acknowledged-BRC

KW - Acknowledged-BRC-13/14

U2 - 10.2217/PGS.13.154

DO - 10.2217/PGS.13.154

M3 - Article

SN - 1462-2416

VL - 14

SP - 1979

EP - 1990

JO - PHARMACOGENOMICS

JF - PHARMACOGENOMICS

IS - 16

ER -

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

Abstract

Keywords

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