Genome-Wide DNA Methylation Meta-analysis in the Brains of Suicide Completers I
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PROVIDER: PRJNA575253 | ENA |
REPOSITORIES: ENA
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Project description:Suicide is the second leading cause of death globally among young people representing a significant global health burden. Although the molecular pathology of suicide remains poorly understood, it has been hypothesised that epigenomic processes may play a role. The objective of this study was to identify suicide-associated DNA methylation changes in the human brain by utilising previously published and unpublished methylomic datasets. We analyzed prefrontal cortex (PFC, n = 211) and cerebellum (CER, n = 114) DNA methylation profiles from suicide completers and non-psychiatric, sudden-death controls, meta-analyzing data from independent cohorts for each brain region separately. We report evidence for altered DNA methylation at several genetic loci in suicide cases compared to controls in both brain regions with suicide-associated differentially methylated positions enriched among functional pathways relevant to neuropsychiatric phenotypes and suicidality, including nervous system development (PFC) and regulation of long-term synaptic depression (CER). In addition, we examined the functional consequences of variable DNA methylation within a PFC suicide-associated differentially methylated region (PSORS1C3 DMR) using a dual luciferase assay and examined expression of nearby genes. DNA methylation within this region was associated with decreased expression of firefly luciferase but was not associated with expression of nearby genes, PSORS1C3 and POU5F1. Our data suggest that suicide is associated with DNA methylation, offering novel insights into the molecular pathology associated with suicidality. DNA from bulk post-mortem brain (human cerebellum) from 33 individuals
2020-03-06 | GSE137223 | GEO
Project description:Suicide is the second leading cause of death globally among young people representing a significant global health burden. Although the molecular pathology of suicide remains poorly understood, it has been hypothesised that epigenomic processes may play a role. The objective of this study was to identify suicide-associated DNA methylation changes in the human brain by utilising previously published and unpublished methylomic datasets. We analyzed prefrontal cortex (PFC, n = 211) and cerebellum (CER, n = 114) DNA methylation profiles from suicide completers and non-psychiatric, sudden-death controls, meta-analyzing data from independent cohorts for each brain region separately. We report evidence for altered DNA methylation at several genetic loci in suicide cases compared to controls in both brain regions with suicide-associated differentially methylated positions enriched among functional pathways relevant to neuropsychiatric phenotypes and suicidality, including nervous system development (PFC) and regulation of long-term synaptic depression (CER). In addition, we examined the functional consequences of variable DNA methylation within a PFC suicide-associated differentially methylated region (PSORS1C3 DMR) using a dual luciferase assay and examined expression of nearby genes. DNA methylation within this region was associated with decreased expression of firefly luciferase but was not associated with expression of nearby genes, PSORS1C3 and POU5F1. Our data suggest that suicide is associated with DNA methylation, offering novel insights into the molecular pathology associated with suicidality. DNA from bulk post-mortem brain (human cerebellum) from 58 individuals
2020-02-27 | GSE137222 | GEO
Project description:Genome-Wide DNA Methylation Meta-analysis in the Brains of Suicide Completers II
| PRJNA575252 | ENA
Project description:Suicide is the second leading cause of death globally among young people representing a significant global health burden. Although the molecular correlates of suicide remains poorly understood, it has been hypothesised that epigenomic processes may play a role. The objective of this study was to identify suicide-associated DNA methylation changes in the human brain by utilising previously published and unpublished methylomic datasets. We analysed prefrontal cortex (PFC, n = 211) and cerebellum (CER, n = 114) DNA methylation profiles from suicide completers and non-psychiatric, sudden-death controls, meta-analysing data from independent cohorts for each brain region separately. We report evidence for altered DNA methylation at several genetic loci in suicide cases compared to controls in both brain regions with suicide-associated differentially methylated positions enriched among functional pathways relevant to psychiatric phenotypes and suicidality, including nervous system development (PFC) and regulation of long-term synaptic depression (CER). In addition, we examined the functional consequences of variable DNA methylation within a PFC suicide-associated differentially methylated region (PSORS1C3 DMR) using a dual luciferase assay and examined expression of nearby genes. DNA methylation within this region was associated with decreased expression of firefly luciferase but was not associated with expression of nearby genes, PSORS1C3 and POU5F1. Our data suggest that suicide is associated with DNA methylation, offering novel insights into the molecular pathology associated with suicidality.
| S-EPMC7031296 | biostudies-literature
Project description:We analyzed the levels of DNA methylation in DNA purified from BA9 of 21 depressed suicide completers and 21 healthy controls, using the Infinium® MethylationEPICBeadChip. The goal of the study was to determine which genes were differentially methylated in neurons between the two groups. We identified1,236 differentially methylated CpGs with a p ≤ 0.001. Gene Ontology and Ingenuity Pathway Analysis were performed to determine classes of genes and pathways associated with the suicide completers.
2022-08-26 | GSE156996 | GEO
Project description:To investige gene expression and methylation changes in the suicide decedents group from postmortem brain tissues
2023-11-10 | GSE243487 | GEO
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
Project description:To investige gene expression and methylation changes in the suicide decedents group from postmortem brain tissues
2023-11-10 | GSE243356 | GEO
Project description:We compared the genome-wide patterns of DNA methylation in the brains of humans to those of our closest evolutionary relative, chimpanzees, using base-pair resolution whole-genome methylation maps of the prefrontal cortex. Our data reveal that the prefrontal cortex is the most heavily methylated among the human tissues examined so far. Nevertheless, hundreds of genes exhibit dramatically reduced levels of promoter DNA methylation in the human brain relative to the chimpanzee brain. Many of these genes are associated with neurological disorders, psychological disorders, and cancers, and are enriched for functions related to cellular metabolic processes and protein binding. Moreover, the majority of these genes exhibit higher expression in the human brain compared to the chimpanzee brain. Profiling DNA methylation map in prefrontal cortex regions of postmortem brains of three humans and three chimpanzees
2012-09-04 | E-GEOD-37202 | biostudies-arrayexpress
Project description:Systematic meta-analysis and replication of genome-wide expression studies identifies molecular pathways of Parkinson's disease. Examination of substantia nigra from postmortem brains of 8 patients with Parkinson's disease (PD).
2011-01-20 | GSE20163 | GEO