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Genome-Wide Methylation Profiling of Schizophrenia

Schizophrenia is one of the major psychiatric disorders. It is a disorder of complex inheritance, involving both heritable and environmental factors. DNA methylation is an inheritable epigenetic modification that stably alters gene expression. We reasoned that genetic modifications that are a result...

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Autores principales: Rukova, B, Staneva, R, Hadjidekova, S, Stamenov, G, Milanova, Toncheva, D
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Macedonian Science of Sciences and Arts 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4413438/
https://www.ncbi.nlm.nih.gov/pubmed/25937794
http://dx.doi.org/10.2478/bjmg-2014-0070
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author Rukova, B
Staneva, R
Hadjidekova, S
Stamenov, G
Milanova,
Toncheva, D
author_facet Rukova, B
Staneva, R
Hadjidekova, S
Stamenov, G
Milanova,
Toncheva, D
author_sort Rukova, B
collection PubMed
description Schizophrenia is one of the major psychiatric disorders. It is a disorder of complex inheritance, involving both heritable and environmental factors. DNA methylation is an inheritable epigenetic modification that stably alters gene expression. We reasoned that genetic modifications that are a result of environmental stimuli could also make a contribution. We have performed 26 high-resolution genome-wide methylation array analyses to determine the methylation status of 27,627 CpG islands and compared the data between patients and healthy controls. Methylation profiles of DNAs were analyzed in six pools: 220 schizophrenia patients; 220 age-matched healthy controls; 110 female schizophrenia patients; 110 age-matched healthy females; 110 male schizophrenia patients; 110 age-matched healthy males. We also investigated the methylation status of 20 individual patient DNA samples (eight females and 12 males. We found significant differences in the methylation profile between schizophrenia and control DNA pools. We found new candidate genes that principally participate in apoptosis, synaptic transmission and nervous system development (GABRA2, LIN7B, CASP3). Methylation profiles differed between the genders. In females, the most important genes participate in apoptosis and synaptic transmission (XIAP, GABRD, OXT, KRT7), whereas in the males, the implicated genes in the molecular pathology of the disease were DHX37, MAP2K2, FNDC4 and GIPC1. Data from the individual methylation analyses confirmed, the gender-specific pools results. Our data revealed major differences in methylation profiles between schizophrenia patients and controls and between male and female patients. The dysregulated activity of the candidate genes could play a role in schizophrenia pathogenesis.
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spelling pubmed-44134382015-05-01 Genome-Wide Methylation Profiling of Schizophrenia Rukova, B Staneva, R Hadjidekova, S Stamenov, G Milanova, Toncheva, D Balkan J Med Genet Original Article Schizophrenia is one of the major psychiatric disorders. It is a disorder of complex inheritance, involving both heritable and environmental factors. DNA methylation is an inheritable epigenetic modification that stably alters gene expression. We reasoned that genetic modifications that are a result of environmental stimuli could also make a contribution. We have performed 26 high-resolution genome-wide methylation array analyses to determine the methylation status of 27,627 CpG islands and compared the data between patients and healthy controls. Methylation profiles of DNAs were analyzed in six pools: 220 schizophrenia patients; 220 age-matched healthy controls; 110 female schizophrenia patients; 110 age-matched healthy females; 110 male schizophrenia patients; 110 age-matched healthy males. We also investigated the methylation status of 20 individual patient DNA samples (eight females and 12 males. We found significant differences in the methylation profile between schizophrenia and control DNA pools. We found new candidate genes that principally participate in apoptosis, synaptic transmission and nervous system development (GABRA2, LIN7B, CASP3). Methylation profiles differed between the genders. In females, the most important genes participate in apoptosis and synaptic transmission (XIAP, GABRD, OXT, KRT7), whereas in the males, the implicated genes in the molecular pathology of the disease were DHX37, MAP2K2, FNDC4 and GIPC1. Data from the individual methylation analyses confirmed, the gender-specific pools results. Our data revealed major differences in methylation profiles between schizophrenia patients and controls and between male and female patients. The dysregulated activity of the candidate genes could play a role in schizophrenia pathogenesis. Macedonian Science of Sciences and Arts 2015-04-10 /pmc/articles/PMC4413438/ /pubmed/25937794 http://dx.doi.org/10.2478/bjmg-2014-0070 Text en © Macedonian Academy of Sciences and Arts This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivs license (http://creativecommons.org/licenses/by-nc-nd/3.0/), which means that the text may be used for non-commercial purposes, provided credit is given to the author.
spellingShingle Original Article
Rukova, B
Staneva, R
Hadjidekova, S
Stamenov, G
Milanova,
Toncheva, D
Genome-Wide Methylation Profiling of Schizophrenia
title Genome-Wide Methylation Profiling of Schizophrenia
title_full Genome-Wide Methylation Profiling of Schizophrenia
title_fullStr Genome-Wide Methylation Profiling of Schizophrenia
title_full_unstemmed Genome-Wide Methylation Profiling of Schizophrenia
title_short Genome-Wide Methylation Profiling of Schizophrenia
title_sort genome-wide methylation profiling of schizophrenia
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4413438/
https://www.ncbi.nlm.nih.gov/pubmed/25937794
http://dx.doi.org/10.2478/bjmg-2014-0070
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