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Cited by 50Schizophrenia research and treatmentEpigenetics and DNA MethylationNeurotransmitter Receptor Influence on Behavior

mRNA Expression and DNA Methylation Analysis of Serotonin Receptor 2A (HTR2A) in the Human Schizophrenic Brain

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Cheah, Sern-Yih, Lawford, Bruce, Young, Ross, Morris, Charles, Voisey, Joanne·2017·Genes
DOI 10.3390/genes8010014PMC PMC5295009
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Abstract

Serotonin receptor 2A (HTR2A) is an important signalling factor implicated in cognitive functions and known to be associated with schizophrenia. The biological significance of HTR2A in schizophrenia remains unclear as molecular analyses including genetic association, mRNA expression and methylation studies have reported inconsistent results. In this study, we examine HTR2A expression and methylation and the interaction with HTR2A polymorphisms 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. HTR2A mRNA levels were reduced by 14% (p = 0.006) in schizophrenia compared to controls. Three CpG sites were hypermethylated in schizophrenia (cg5 p = 0.028, cg7 p = 0.021, cg10 p = 0.017) and HTR2A polymorphisms 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 between HTR2A DNA methylation and mRNA expression. The results were nominally significant but did not survive the rigorous Benjamini-Hochberg correction for multiple testing. Differential HTR2A expression in schizophrenia in our study may be the result of the combined effect of multiple differentially methylated CpG sites. Epigenetic HTR2A regulation may alter brain function, which contributes to the development of schizophrenia.

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  • Candidate gene studies in SCZ and BD across various tissues show elevated DNAm of the 5-HTR1A and 5-HTR2A genes respectively.

    “Candidate gene studies in SCZ and BD across various tissues (Abdolmaleky et al., 2011; Carrard, Salzmann, Malafosse, & Karege, 2011; Cheah, Lawford, Young, Morris, & Voisey, 2017) show elevated DNAm of the 5-HTR1A and 5-HTR2A genes respectively.”

    From Can epigenetics shine a light on the biological pathways underlying major mental disorders? (2022) · cites this paper as Cheah, Lawford, Young, Morris, & Voisey, 2017

    The Discussion and Conclusions report hypermethylation of HTR2A promoter CpG sites in schizophrenia brain samples. The source does not establish the sentence’s respective pairing of schizophrenia with 5-HTR1A and bipolar disorder with 5-HTR2A, nor does this study examine various tissues. (LLM, conf=0.88)

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Sorted by citations

Authors
Cheah, S.-Y., Lawford, B., Young, R., Morris, C., & Voisey, J.
Affiliations
Queensland University of Technology (AU)
Corresponding author
Voisey, Joanne
ORCID
Venue
Genes
Publisher
MDPI AG
Published
2017-01-04
Volume
8
Issue
1
Pages
14
ISSN
2073-4425 (ISSN-L)
DOI
10.3390/genes8010014
PMC
PMC5295009
OpenAlex
W2571471875
Cited by
50
References
1
Citations by year
2026: 2 · 2025: 8 · 2024: 3 · 2023: 5 · 2022: 5 · 2021: 6 · 2020: 10 · 2019: 6 · 2018: 3 · 2017: 2
FWCI
4.57
Type
journal article
Language
en
Open access
Licence
Locations
  • Genes (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • QUT ePrints (Queensland University of Technology) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Faculty of Health; Institute of Health and Biomedical Innovation
Funders
Queensland University of Technology
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
5-HT2A receptor, HTR2A, schizophrenia, DNA methylation, mRNA expression, rs6313, promoter CpG sites, epigenetic regulation, gene expression-methylation correlation, postmortem brain, genetic association

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