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Single-nucleus chromatin accessibility profiling identifies cell types and functional variants contributing to major depression

ABSTRACT: Single-nucleus chromatin accessibility profiling identifies cell types and functional variants contributing to major depression

PROVIDER: PRJNA1032938 | ENA |

REPOSITORIES: ENA

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Single-nucleus chromatin accessibility profiling identifies cell types and functional variants contributing to major depression

Project description:We performed high-throughput snATAC-seq using the 10X Genomics Chromium platform on archived post-mortem dorsolateral prefrontal cortex (BA9) tissue in MDD subjects who died by suicide and neurotypical control subjects to identify cell-type specific differentially accessible chromatin regions. We further combined snATAC-seq with previously generated snRNA-seq data from the same subjects to generate high-resolution multi-modal accessibility and expression atlas of cortical cells. This identified accessible chromatin regions potentially regulating expression of genes. Further, MDD-associated genetic risk variants were examined for their allele-specific effects on chromatin accessibility and transcription factors binding sites in cell type speciifc manner, elucdiating target risk genes and pathways associated with MDD.

2025-01-21 | GSE246443 | GEO

Major depression MDD suicide brain study

Project description: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.

2016-11-01 | GSE88890 | GEO

Whole Genome Sequencing in Psychotic Major Depression

Project description:Whole Genome Sequencing in Psychotic Major Depression

| PRJNA476193 | ENA

Whole Genome Sequencing in Psychotic Major Depression

Project description:Whole Genome Sequencing in Psychotic Major Depression

| PRJNA476194 | ENA

Peripheral whole blood: Healthy control and Major depression disorder patients

Project description:Transcriptional profiling in the whole blood samples of healthy controls and major depression disorder (MDD) patients who have never been treated with depression medication. Samples included 20 healthy controls and 20 MDD patients who have never been treated with depression medication. Goal was to discover the differentially expressed genes.

2022-07-18 | GSE201332 | GEO

Expression data from peripheral blood lymphocytes of major depression, subsyndromal symptomatic depression, and healthy controls

2012-03-21 | GSE32280 | GEO

Expression data from peripheral blood lymphocytes of major depression, subsyndromal symptomatic depression, and healthy controls

Project description:Several studies have suggested that SSD is a transitory phenomena in the depression spectrum and is thus considered a subtype of depression. However, the pathophysioloy of depression remain largely obscure and studies on SSD are limited. The present study compared the expression profile and made the classification with the leukocytes by using whole-genome cRNA microarrays among drug-free first-episode subjects with SSD, MDD, and healthy controls. We used microarrays to detail the global programme of gene expression to develop blood-based gene expression profiles models for classification of subsyndromal symptomatic depression and major depressive disorder The present study compared the expression profile and made the classification with the leukocytes by using whole-genome cRNA microarrays among drug-free first-episode subjects with SSD, MDD, and matched controls (8 subjects in each group). Support vector machines (SVMs) were utilized for training and testing on candidate signature expression profiles from signature selection step.

2012-03-21 | E-GEOD-32280 | biostudies-arrayexpress

MicroRNAs as diagnostic biomarkers for major depression

Project description:Blood samples taken from healthy controls and patients with major depression were analyzed for differences in microRNA expression. Patients were treated with either electroconvulsive therapy or ketamine and samples were again analyzed to determine if these treatments affected microRNA expression. Baseline microRNA expression profiles were studied to see if they could predict treatment response.

2016-08-31 | GSE81152 | GEO

Integration of Genomics & Transcriptomics in Normal Twins & Major Depression

Project description:Integration of Genomics & Transcriptomics in Normal Twins & Major Depression

| PRJNA157213 | ENA

Transcription profiling of human entorhinal cortex cells from suicide patients with major depression.

Project description:RNAs were extracted from entorhinal cortex of human suicide patients with major depression and matched control subjects. The transcription profile was investigated by Agilent microarray platform and quantitative real-time PCR to reveal alterations in neuronal functions in this brain region.

2010-12-31 | E-MEXP-2607 | biostudies-arrayexpress

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