Cargando…

DNA methylation differences in monozygotic twin pairs discordant for schizophrenia identifies psychosis related genes and networks

BACKGROUND: Despite their singular origin, monozygotic twin pairs often display discordance for complex disorders including schizophrenia. It is a common (1%) and often familial disease with a discordance rate of ~50% in monozygotic twins. This high discordance is often explained by the role of yet...

Descripción completa

Detalles Bibliográficos
Autores principales: Castellani, Christina A, Laufer, Benjamin I, Melka, Melkaye G, Diehl, Eric J, O’Reilly, Richard L, Singh, Shiva M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4494167/
https://www.ncbi.nlm.nih.gov/pubmed/25943100
http://dx.doi.org/10.1186/s12920-015-0093-1
_version_ 1782380036088659968
author Castellani, Christina A
Laufer, Benjamin I
Melka, Melkaye G
Diehl, Eric J
O’Reilly, Richard L
Singh, Shiva M
author_facet Castellani, Christina A
Laufer, Benjamin I
Melka, Melkaye G
Diehl, Eric J
O’Reilly, Richard L
Singh, Shiva M
author_sort Castellani, Christina A
collection PubMed
description BACKGROUND: Despite their singular origin, monozygotic twin pairs often display discordance for complex disorders including schizophrenia. It is a common (1%) and often familial disease with a discordance rate of ~50% in monozygotic twins. This high discordance is often explained by the role of yet unknown environmental, random, and epigenetic factors. The involvement of DNA methylation in this disease appears logical, but remains to be established. METHODS: We have used blood DNA from two pairs of monozygotic twins discordant for schizophrenia and their parents in order to assess genome-wide methylation using a NimbleGen Methylation Promoter Microarray. RESULTS: The genome-wide results show that differentially methylated regions (DMRs) exist between members representing discordant monozygotic twins. Some DMRs are shared with parent(s) and others appear to be de novo. We found twenty-seven genes affected by DMR changes that were shared in the affected member of two discordant monozygotic pairs from unrelated families. Interestingly, the genes affected by pair specific DMRs share specific networks. Specifically, this study has identified two networks; “cell death and survival” and a “cellular movement and immune cell trafficking”. These two networks and the genes affected have been previously implicated in the aetiology of schizophrenia. CONCLUSIONS: The results are compatible with the suggestion that DNA methylation may contribute to the discordance of monozygotic twins for schizophrenia. Also, this may be accomplished by the direct effect of gene specific methylation changes on specific biological networks rather than individual genes. It supports the extensive genetic, epigenetic and phenotypic heterogeneity implicated in schizophrenia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12920-015-0093-1) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-4494167
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-44941672015-07-08 DNA methylation differences in monozygotic twin pairs discordant for schizophrenia identifies psychosis related genes and networks Castellani, Christina A Laufer, Benjamin I Melka, Melkaye G Diehl, Eric J O’Reilly, Richard L Singh, Shiva M BMC Med Genomics Research Article BACKGROUND: Despite their singular origin, monozygotic twin pairs often display discordance for complex disorders including schizophrenia. It is a common (1%) and often familial disease with a discordance rate of ~50% in monozygotic twins. This high discordance is often explained by the role of yet unknown environmental, random, and epigenetic factors. The involvement of DNA methylation in this disease appears logical, but remains to be established. METHODS: We have used blood DNA from two pairs of monozygotic twins discordant for schizophrenia and their parents in order to assess genome-wide methylation using a NimbleGen Methylation Promoter Microarray. RESULTS: The genome-wide results show that differentially methylated regions (DMRs) exist between members representing discordant monozygotic twins. Some DMRs are shared with parent(s) and others appear to be de novo. We found twenty-seven genes affected by DMR changes that were shared in the affected member of two discordant monozygotic pairs from unrelated families. Interestingly, the genes affected by pair specific DMRs share specific networks. Specifically, this study has identified two networks; “cell death and survival” and a “cellular movement and immune cell trafficking”. These two networks and the genes affected have been previously implicated in the aetiology of schizophrenia. CONCLUSIONS: The results are compatible with the suggestion that DNA methylation may contribute to the discordance of monozygotic twins for schizophrenia. Also, this may be accomplished by the direct effect of gene specific methylation changes on specific biological networks rather than individual genes. It supports the extensive genetic, epigenetic and phenotypic heterogeneity implicated in schizophrenia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12920-015-0093-1) contains supplementary material, which is available to authorized users. BioMed Central 2015-05-06 /pmc/articles/PMC4494167/ /pubmed/25943100 http://dx.doi.org/10.1186/s12920-015-0093-1 Text en © Castellani et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Castellani, Christina A
Laufer, Benjamin I
Melka, Melkaye G
Diehl, Eric J
O’Reilly, Richard L
Singh, Shiva M
DNA methylation differences in monozygotic twin pairs discordant for schizophrenia identifies psychosis related genes and networks
title DNA methylation differences in monozygotic twin pairs discordant for schizophrenia identifies psychosis related genes and networks
title_full DNA methylation differences in monozygotic twin pairs discordant for schizophrenia identifies psychosis related genes and networks
title_fullStr DNA methylation differences in monozygotic twin pairs discordant for schizophrenia identifies psychosis related genes and networks
title_full_unstemmed DNA methylation differences in monozygotic twin pairs discordant for schizophrenia identifies psychosis related genes and networks
title_short DNA methylation differences in monozygotic twin pairs discordant for schizophrenia identifies psychosis related genes and networks
title_sort dna methylation differences in monozygotic twin pairs discordant for schizophrenia identifies psychosis related genes and networks
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4494167/
https://www.ncbi.nlm.nih.gov/pubmed/25943100
http://dx.doi.org/10.1186/s12920-015-0093-1
work_keys_str_mv AT castellanichristinaa dnamethylationdifferencesinmonozygotictwinpairsdiscordantforschizophreniaidentifiespsychosisrelatedgenesandnetworks
AT lauferbenjamini dnamethylationdifferencesinmonozygotictwinpairsdiscordantforschizophreniaidentifiespsychosisrelatedgenesandnetworks
AT melkamelkayeg dnamethylationdifferencesinmonozygotictwinpairsdiscordantforschizophreniaidentifiespsychosisrelatedgenesandnetworks
AT diehlericj dnamethylationdifferencesinmonozygotictwinpairsdiscordantforschizophreniaidentifiespsychosisrelatedgenesandnetworks
AT oreillyrichardl dnamethylationdifferencesinmonozygotictwinpairsdiscordantforschizophreniaidentifiespsychosisrelatedgenesandnetworks
AT singhshivam dnamethylationdifferencesinmonozygotictwinpairsdiscordantforschizophreniaidentifiespsychosisrelatedgenesandnetworks