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Series GSE88890 Query DataSets for GSE88890
Status Public on Nov 01, 2016
Title Major depression MDD suicide brain study
Organism Homo sapiens
Experiment type Methylation profiling by array
Summary Background: Major Depressive Disorder (MDD) represents a major social and economic health issue and constitutes a major risk factor for MDD suicide. The molecular pathology of suicidal depression remains poorly understood, although it has been hypothesized that regulatory genomic processes are involved in the pathology of both MDD and suicidality.
Methods: Genome-wide patterns of DNA methylation were assessed in depressed MDD suicide completers (n=20) and compared to non-psychiatric, sudden-death controls (n=20) using tissue from two cortical brain regions (Brodmann Area 11 (BA11) and Brodmann Area 25 (BA25)). Analyses focussed on identifying differentially methylated regions (DMRs) associated with suicidal depression, and epigenetic variation was explored in the context of polygenic risk scores for major depression and MDD suicide. Weighted gene co-methylation network analysis was used to identify modules of co-methylated loci associated with depressed MDD suicide completers and polygenic burden for MDD and MDD suicide attempt.
Results: We identified a DMR upstream of the PSORS1C3 gene, subsequently validated using bisulfite-pyrosequencing and replicated in a second set of MDD suicide samples, which is characterized by significant hypomethylation in both cortical brain regions in MDD MDD suicide cases. We also identified discrete modules of co-methylated loci associated with polygenic risk burden for MDD suicide attempt, but not major depression. MDD suicide-associated co-methylation modules were enriched among gene networks implicating biological processes relevant to depression and suicidality, including nervous system development and mitochondria function.
Conclusions: Our data suggest there are coordinated changes in DNA methylation associated with MDD suicide that may offer novel insights into the molecular pathology associated with depressed MDD suicide completers.
Overall design Tissue (n=75) from two regions of the cortex (Brodmann area 11 (BA11, n=40) and Brodmann area 25 (BA25, n=35)) from 20 MDD MDD suicide cases and 20 non-psychiatric sudden death controls
Contributor(s) Murphy TM, Crawford B, Dempster EL, Hannon E, Burrage J, Turecki G, Kaminsky Z, Mill J
Citation(s) 28045465
Submission date Oct 18, 2016
Last update date Mar 22, 2019
Contact name Therese M Murphy
Organization name University of Exeter
Department University of Exeter Medical School
Street address RILD building
City Exeter
ZIP/Postal code EX2 5DW
Country United Kingdom
Platforms (1)
GPL13534 Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)
Samples (75)
GSM2350798 184_BA25
GSM2350799 179_BA25
GSM2350800 20_BA25
BioProject PRJNA349028

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE88890_RAW.tar 183.1 Mb (http)(custom) TAR
GSE88890_detectionP.csv.gz 1.7 Mb (ftp)(http) CSV
GSE88890_methylatedIntensities.csv.gz 68.1 Mb (ftp)(http) CSV
GSE88890_normalisedBetas.csv.gz 245.6 Mb (ftp)(http) CSV
GSE88890_rawBetas.csv.gz 86.5 Mb (ftp)(http) CSV
GSE88890_unmethylatedIntensities.csv.gz 69.3 Mb (ftp)(http) CSV
Processed data included within Sample table
Processed data are available on Series record

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