Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

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

Malki, K, Pain, O, Tosto, M G, Du Rietz, E, Carboni, L and Schalkwyk, L C 2018. Identification of genes and gene pathways associated with major depressive disorder by integrative brain analysis of rat and human prefrontal cortex transcriptomes. Translational Psychiatry 5 (3) , e519. 10.1038/tp.2015.15

[img]
Preview
PDF - Published Version
Available under License Creative Commons Attribution.

Download (1MB) | Preview

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 probe sets tagged the expression profile of 18 human genes (11 upregulated and seven downregulated). Using an integrative rat–human study, a number of convergent genes that may have a role in pathogenesis of MDD were uncovered. Eighty percent of these genes were functionally associated with a key stress response signalling cascade, involving NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), AP-1 (activator protein 1) and ERK/MAPK, which has been systematically associated with MDD, neuroplasticity and neurogenesis.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Publisher: Nature Publishing Group: Open Access Journals - Option B / Nature Publishing Group
ISSN: 2158-3188
Date of First Compliant Deposit: 17 April 2018
Date of Acceptance: 12 January 2015
Last Modified: 16 May 2018 11:00
URI: http://orca-mwe.cf.ac.uk/id/eprint/110746

Citation Data

Cited 21 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item