Identification of genes and gene pathways associated with major depressive disorder by integrative brain analysis of rat and human prefrontal cortex transcriptomes

Translational Psychiatry
Karim MalkiLeonard C Schalkwyk

Abstract

Despite moderate heritability estimates, progress in uncovering the molecular substrate underpinning major depressive disorder (MDD) has been slow. In this study, we used prefrontal cortex (PFC) gene expression from a genetic rat model of MDD to inform probe set prioritization in PFC in a human post-mortem study to uncover genes and gene pathways associated with MDD. Gene expression differences between Flinders sensitive (FSL) and Flinders resistant (FRL) rat lines were statistically evaluated using the RankProd, non-parametric algorithm. Top ranking probe sets in the rat study were subsequently used to prioritize orthologous selection in a human PFC in a case-control post-mortem study on MDD from the Stanley Brain Consortium. Candidate genes in the human post-mortem study were then tested against a matched control sample using the RankProd method. A total of 1767 probe sets were differentially expressed in the PFC between FSL and FRL rat lines at (q⩽0.001). A total of 898 orthologous probe sets was found on Affymetrix's HG-U95A chip used in the human study. Correcting for the number of multiple, non-independent tests, 20 probe sets were found to be significantly dysregulated between human cases and controls at q⩽0.05. These pr...Continue Reading

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Citations

Apr 20, 2016·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Karim MalkiMaria Grazia Tosto
Jun 15, 2016·Translational Psychiatry·K MalkiM G Tosto
Oct 30, 2016·Neuroscience and Biobehavioral Reviews·Liliana G CiobanuBernhard T Baune
Sep 1, 2016·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Bhaskar RoyYogesh Dwivedi
Oct 4, 2016·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Karim MalkiMark Herbster
May 4, 2017·Developmental Neuropsychology·Yanfang WangKerang Zhang
Aug 21, 2019·Nature Neuroscience·Zachary S LorschEric J Nestler
Aug 30, 2017·Frontiers in Molecular Neuroscience·Mylène HervéEl Chérif Ibrahim
Jan 16, 2019·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Joshua Hyong-Jin ChoSteve W Cole
Dec 11, 2019·Neuroscience and Biobehavioral Reviews·Corey B PuryearConnie Sanchez
Nov 18, 2018·British Journal of Anaesthesia·K Hirota, D G Lambert

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Datasets Mentioned

BETA
GSE12654
GS2088

Methods Mentioned

BETA
chip
PCR

Software Mentioned

RankProd
Affymetrix
Ingenuity Pathway Analysis ( IPA )
IPA
GENDEP
NetAffx
inSilicoMerging

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