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

Serotonin receptor 2A ( ) is an important signalling factor implicated in cognitive functions and known to be associated with schizophrenia. The biological significance of in schizophrenia remains unclear as molecular analyses including genetic association, mRNA expression and methylation studies have reported inconsistent results. In this study, we examine expression and methylation and the interaction with 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. mRNA levels were reduced by 14% ( = 0.006) in schizophrenia compared to controls. Three CpG sites were hypermethylated in schizophrenia (cg5 = 0.028, cg7 = 0.021, cg10 = 0.017) and polymorphisms rs6314 ( = 0.008) and rs6313 ( = 0.026) showed genetic association with schizophrenia. Differential DNA methylation was associated with rs6314 and rs6313. There was a strong correlation between DNA methylation and mRNA expression. The results were nominally significant but did not survive the rigorous Benjamini-Hochberg correction for multiple testing. Differential expression in schizophrenia in our study may be the result of the combined effect of multiple differentially methylated CpG sites. Epigenetic regulation may alter brain function, which contributes to the development of schizophrenia.