Balkan Journal of Medical Genetics

GENOME-WIDE METHYLATION PROFILING OF SCHIZOPHRENIA
Rukova B1, Staneva R1, Hadjidekova S1, Stamenov G2, Milanova V3, Toncheva D1,
*Corresponding Author: Professor Draga Toncheva, Department of Medical Genetics, Medical University of Sofia, 1431 2 Zdrave Str., Sofia, Bulgaria. Tel./Fax: +35929520357. Email: dragatoncheva@ gmail.com
page: 15

INTRODUCTION

Schizophrenia is a severe psychiatric disorder, characterized by debilitating behavioral abnormalities, delusions, hallucinations and negative symptoms [1]. It is an etiologically complex disorder, involving both heritable and non heritable factors, with heritability estimates of up to 81.0% [2]. It is believed that the disorder is due to early neurodevelopmental factors, imbalances in neurotransmitter signaling, together with obstetric complications, infections, stress and trauma [3,4]. In the absence of established diagnostic biological markers, diagnosis of schizophrenia relies on examination of mental state by a clinical interview [5]. DNA methylation is a basic epigenetic modification, important for normal development in higher organisms. It alters the gene expression without modification of the primary DNA sequence and is heritable through the cell [6]. It involves conversion of the cytosine to 5-methylcytosine by means of DNA methyltransferases [6]. In eukaryotes, methylation is most commonly found in CG rich areas of DNA, called CpG islands [7]. The epigenetic processes are dynamic and allow the cells to respond reversibly and in a precise way to environmental stimuli, but also preserve cell type specific gene programs. Epigenetic changes over time display familial clustering [8]. This could explain the clustering of some common diseases in families, so the epigenetic pattern could be implicated in transmitting “predisposition” over generations. DNA methylation can be associated with the transcription start sites of genes or can be found in the gene bodies, intergenic or in distant regulatory regions. The position of the methylation affects its relationship to gene expression level. Methylation in the immediate vicinity of the transcription start site blocks initiation, while methylation inside the gene stimulates transcription elongation. So it is suggested that gene body methylation may have an effect on splicing. It is supposed that the methylation in repetitive regions is important for chromosomal and genomic stability, and probably represses transposable element expression. Yet the role of DNA methylation in modifying the action of regulatory elements such as enhancers is not well established [9,10]. There is evidence of DNA methylation aberrations in a wide variety of brain disorders such as mental retardation, Angelman and Prader-Willi syndromes, fragile X syndrome, gliomas and neuroectodermal tumors. Yet there are no conclusive studies about DNA methylation in major psychotic disorders such as schizophrenia and bipolar disorder [11,12]. Studies of the Bulgarian schizophrenia population have implicated common and rare genetic factors [13-16]. Here we use the same large clinical cohort and propose a role of epigenetic modifiers of gene expression in the development and progression of the disease and use cohort. Epidemiological data as variable age of onset between males and females, advanced paternal age, in utero nutritional deficiency, viral exposure and hypoxia, support the importance of “epigenetic” modifications. Because of the dynamic nature and potential reversibility of DNA methylation, the study of its mechanisms is very important for clinical psychiatry and for identifying new targets for prevention and intervention. The aim of our study was to investigate the whole genome methylation profile to find specific differentially methylated regions (DMRs) for schizophrenia patients. We tried to find genderspecific differences in methylation pattern. Here we report our best candidate genes with DMRs for association with schizophrenia.

Number 27 VOL. 27 (1), 2024	Number 26 Number 26 VOL. 26(2), 2023 All in one
Number 26 VOL. 26(2), 2023	Number 26 VOL. 26, 2023 Supplement
Number 26 VOL. 26(1), 2023	Number 25 VOL. 25(2), 2022
Number 25 VOL. 25 (1), 2022	Number 24 VOL. 24(2), 2021
Number 24 VOL. 24(1), 2021	Number 23 VOL. 23(2), 2020
Number 22 VOL. 22(2), 2019	Number 22 VOL. 22(1), 2019
Number 22 VOL. 22, 2019 Supplement	Number 21 VOL. 21(2), 2018
Number 21 VOL. 21 (1), 2018	Number 21 VOL. 21, 2018 Supplement
Number 20 VOL. 20 (2), 2017	Number 20 VOL. 20 (1), 2017
Number 19 VOL. 19 (2), 2016	Number 19 VOL. 19 (1), 2016
Number 18 VOL. 18 (2), 2015	Number 18 VOL. 18 (1), 2015
Number 17 VOL. 17 (2), 2014	Number 17 VOL. 17 (1), 2014
Number 16 VOL. 16 (2), 2013	Number 16 VOL. 16 (1), 2013
Number 15 VOL. 15 (2), 2012	Number 15 VOL. 15, 2012 Supplement
Number 15 Vol. 15 (1), 2012	Number 14 14 - Vol. 14 (2), 2011
Number 14 The 9th Balkan Congress of Medical Genetics	Number 14 14 - Vol. 14 (1), 2011
Number 13 Vol. 13 (2), 2010	Number 13 Vol.13 (1), 2010
Number 12 Vol.12 (2), 2009	Number 12 Vol.12 (1), 2009
Number 11 Vol.11 (2),2008	Number 11 Vol.11 (1),2008
Number 10 Vol.10 (2), 2007	Number 10 10 (1),2007
Number 9 1&2, 2006	Number 9 3&4, 2006
Number 8 1&2, 2005	Number 8 3&4, 2004
Number 7 1&2, 2004	Number 6 3&4, 2003
Number 6 1&2, 2003	Number 5 3&4, 2002
Number 5 1&2, 2002	Number 4 Vol.3 (4), 2000
Number 4 Vol.2 (4), 1999	Number 4 Vol.1 (4), 1998
Number 4 3&4, 2001	Number 4 1&2, 2001
Number 3 Vol.3 (3), 2000	Number 3 Vol.2 (3), 1999
Number 3 Vol.1 (3), 1998	Number 2 Vol.3(2), 2000
Number 2 Vol.1 (2), 1998	Number 2 Vol.2 (2), 1999
Number 1 Vol.3 (1), 2000	Number 1 Vol.2 (1), 1999
Number 1 Vol.1 (1), 1998

About the journal ::: Editorial ::: Subscription ::: Information for authors ::: Contact