title: mRNA Expression and DNA Methylation Analysis of Serotonin Receptor 2A (HTR2A) in the Human Schizophrenic Brain.
abstract: Serotonin receptor 2A (HTR2A) is an important signalling factor implicated in cognitive functions and known to be associated with schizophrenia. The biological significance ofHTR2Ain schizophrenia remains unclear as molecular analyses including genetic association, mRNA expression and methylation studies have reported inconsistent results. In this study, we examineHTR2Aexpression and methylation and the interaction withHTR2Apolymorphisms to identify their biological significance in schizophrenia. Subjects included 25 schizophrenia and 25 control post-mortem brain samples. Genotype and mRNA data was generated by transcriptome sequencing. DNA methylation profiles were generated for CpG sites within promoter-exon I region. Expression, genotype and methylation data were examined for association with schizophrenia.HTR2AmRNA levels were reduced by 14% (p= 0.006) in schizophrenia compared to controls. Three CpG sites were hypermethylated in schizophrenia (cg5p= 0.028, cg7p= 0.021, cg10p= 0.017) andHTR2Apolymorphisms rs6314 (p= 0.008) and rs6313 (p= 0.026) showed genetic association with schizophrenia. Differential DNA methylation was associated with rs6314 and rs6313. There was a strong correlation betweenHTR2ADNA methylation and mRNA expression. The results were nominally significant but did not survive the rigorous Benjamini-Hochberg correction for multiple testing. DifferentialHTR2Aexpression in schizophrenia in our study may be the result of the combined effect of multiple differentially methylated CpG sites. EpigeneticHTR2Aregulation may alter brain function, which contributes to the development of schizophrenia.
authors.affiliation: School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Ave., Kelvin Grove, Queensland 4059, Australia. sern.cheah@hdr.qut.edu.au.
authors.forename: Sern-Yih
authors.initials: SY
authors.lastname: Cheah
authors.affiliation: School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Ave., Kelvin Grove, Queensland 4059, Australia. lawford.b@gmail.com.|Discipline of Psychiatry, Royal Brisbane and Women's Hospital, Herston, Queensland 4006, Australia. lawford.b@gmail.com.
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Lawford
authors.affiliation: Faculty of Health, Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Ave., Kelvin Grove, Queensland 4059, Australia. rm.young@qut.edu.au.
authors.forename: Ross McD
authors.initials: RM
authors.lastname: Young
authors.affiliation: School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Ave., Kelvin Grove, Queensland 4059, Australia. p.morris@qut.edu.au.
authors.forename: Charles P
authors.initials: CP
authors.lastname: Morris
authors.affiliation: School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Ave., Kelvin Grove, Queensland 4059, Australia. j.voisey@qut.edu.au.
authors.forename: Joanne
authors.initials: J
authors.lastname: Voisey
keywords: DNA methylation; HTR2A; epigenetics; mRNA expression; rs6313; rs6314; schizophrenia association