Methylomic profiling of cortex samples from completed suicide cases implicates a role for PSORS1C3 in major depression and suicide

2.50
Hdl Handle:
http://hdl.handle.net/11287/620195
Title:
Methylomic profiling of cortex samples from completed suicide cases implicates a role for PSORS1C3 in major depression and suicide
Authors:
Murphy, T M; Crawford, B; Dempster, E L; Hannon, E; Burrage, J; Turecki, G; Kaminsky, Z; Mill, Jonathan
Abstract:
Major depressive disorder (MDD) represents a major social and economic health issue and constitutes a major risk factor for suicide. The molecular pathology of suicidal depression remains poorly understood, although it has been hypothesised that regulatory genomic processes are involved in the pathology of both MDD and suicidality. In this study, genome-wide patterns of DNA methylation were assessed in depressed suicide completers (n=20) and compared with non-psychiatric, sudden-death controls (n=20) using tissue from two cortical brain regions (Brodmann Area 11 (BA11) and Brodmann Area 25 (BA25)). Analyses focused on identifying differentially methylated regions (DMRs) associated with suicidal depression and epigenetic variation were explored in the context of polygenic risk scores for major depression and suicide. Weighted gene co-methylation network analysis was used to identify modules of co-methylated loci associated with depressed suicide completers and polygenic burden for MDD and suicide attempt. We identified a DMR upstream of the PSORS1C3 gene, subsequently validated using bisulfite pyrosequencing and replicated in a second set of suicide samples, which is characterised by significant hypomethylation in both cortical brain regions in MDD suicide cases. We also identified discrete modules of co-methylated loci associated with polygenic risk burden for suicide attempt, but not major depression. 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. Our data suggest that there are coordinated changes in DNA methylation associated with suicide that may offer novel insights into the molecular pathology associated with depressed suicide completers.
Citation:
Methylomic profiling of cortex samples from completed suicide cases implicates a role for PSORS1C3 in major depression and suicide 2017, 7 (1):e989 Translational Psychiatry
Publisher:
Nature
Journal:
Translational Psychiatry
Issue Date:
3-Jan-2017
URI:
http://hdl.handle.net/11287/620195
DOI:
10.1038/tp.2016.249
Additional Links:
http://www.nature.com/doifinder/10.1038/tp.2016.249
Note:
This article is freely available via Open Access. Click on the Additional Link above to access the full-text via the publisher's site.
Type:
Journal Article
Language:
en
ISSN:
2158-3188
Appears in Collections:
Honorary contracts publications; 2017 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorMurphy, T Men
dc.contributor.authorCrawford, Ben
dc.contributor.authorDempster, E Len
dc.contributor.authorHannon, Een
dc.contributor.authorBurrage, Jen
dc.contributor.authorTurecki, Gen
dc.contributor.authorKaminsky, Zen
dc.contributor.authorMill, Jonathanen
dc.date.accessioned2017-01-19T12:06:28Z-
dc.date.available2017-01-19T12:06:28Z-
dc.date.issued2017-01-03-
dc.identifier.citationMethylomic profiling of cortex samples from completed suicide cases implicates a role for PSORS1C3 in major depression and suicide 2017, 7 (1):e989 Translational Psychiatryen
dc.identifier.issn2158-3188-
dc.identifier.doi10.1038/tp.2016.249-
dc.identifier.urihttp://hdl.handle.net/11287/620195-
dc.description.abstractMajor depressive disorder (MDD) represents a major social and economic health issue and constitutes a major risk factor for suicide. The molecular pathology of suicidal depression remains poorly understood, although it has been hypothesised that regulatory genomic processes are involved in the pathology of both MDD and suicidality. In this study, genome-wide patterns of DNA methylation were assessed in depressed suicide completers (n=20) and compared with non-psychiatric, sudden-death controls (n=20) using tissue from two cortical brain regions (Brodmann Area 11 (BA11) and Brodmann Area 25 (BA25)). Analyses focused on identifying differentially methylated regions (DMRs) associated with suicidal depression and epigenetic variation were explored in the context of polygenic risk scores for major depression and suicide. Weighted gene co-methylation network analysis was used to identify modules of co-methylated loci associated with depressed suicide completers and polygenic burden for MDD and suicide attempt. We identified a DMR upstream of the PSORS1C3 gene, subsequently validated using bisulfite pyrosequencing and replicated in a second set of suicide samples, which is characterised by significant hypomethylation in both cortical brain regions in MDD suicide cases. We also identified discrete modules of co-methylated loci associated with polygenic risk burden for suicide attempt, but not major depression. 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. Our data suggest that there are coordinated changes in DNA methylation associated with suicide that may offer novel insights into the molecular pathology associated with depressed suicide completers.en
dc.language.isoenen
dc.publisherNatureen
dc.relation.urlhttp://www.nature.com/doifinder/10.1038/tp.2016.249en
dc.rightsArchived with thanks to Translational Psychiatryen
dc.subjectWessex Classification Subject Headings::Psychologyen
dc.titleMethylomic profiling of cortex samples from completed suicide cases implicates a role for PSORS1C3 in major depression and suicideen
dc.typeJournal Articleen
dc.identifier.journalTranslational Psychiatryen
dc.description.noteThis article is freely available via Open Access. Click on the Additional Link above to access the full-text via the publisher's site.en
dc.type.versionPublisheden
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