DNA methylation schizophrenia association Val66Met BDNF mRNA expression
Objectives: To examine the combined effect of the BDNF Val66Met (rs6265) polymorphism and BDNF DNA methylation on transcriptional regulation of the BDNF gene.
Methods: DNA methylation profiles were generated for CpG sites proximal to Val66Met, within BDNF promoter I and exon V for prefrontal cortex samples from 25 schizophrenia and 25 control subjects. Val66Met genotypes and BDNF mRNA expression data were generated by transcriptome sequencing. Expression, methylation and genotype data were correlated and examined for association with schizophrenia.
Results: There was 43% more of the BDNF V-VIII-IX transcript in schizophrenia samples. BDNF mRNA expression and DNA methylation of seven CpG sites were not associated with schizophrenia after accounting for age and PMI effects. BDNF mRNA expression and DNA methylation were not altered by Val66Met after accounting for age and PMI effects. DNA methylation of one CpG site had a marginally significant positive correlation with mRNA expression in schizophrenia subjects.
Conclusions: Schizophrenia risk was not associated with differential BDNF mRNA expression and DNA methylation. A larger age-matched cohort with comprehensive clinical history is required to accurately identify the effects of genotype, mRNA expression and DNA methylation on schizophrenia risk.
Details
Title
Expression and methylation of BDNF in the human brain in schizophrenia
Authors
Sern-Yih Cheah (Author) - The University of Queensland
Robert McLeay (Author) - Queensland University of Technology
Leesa F Wockner (Author) - QIMR Berghofer Medical Research Institute
Bruce R Lawford (Author) - Queensland University of Technology
Ross Young (Author) - Queensland University of Technology
Charles P Morris (Author) - Queensland University of Technology
Joanne Voisey (Author) - Queensland University of Technology
Publication details
World Journal of Biological Psychiatry, Vol.18(5), pp.392-400
Publisher
Taylor & Francis
Date published
2017
DOI
10.1080/15622975.2016.1245443
ISSN
1814-1412; 1562-2975
PMID
27712141
Copyright note
Copyright (c) 2017. This is an Accepted Manuscript of an article published by Taylor & Francis in World Journal of Biological Psychiatry on 2017, available online: http://www.tandfonline.com/10.1080/15622975.2016.1245443
Organisation Unit
University of the Sunshine Coast, Queensland; Office of the Deputy Vice-Chancellor (Research and Innovation)