DDR1 methylation is associated with bipolar disorder and the isoform expression and methylation of myelin genes

Epigenomics. 2021 Jun;13(11):845-858. doi: 10.2217/epi-2021-0006. Epub 2021 May 4.

Abstract

Aim: To investigate DDR1 methylation in the brains of bipolar disorder (BD) patients and its association with DDR1 mRNA levels and comethylation with myelin genes. Materials & methods: Genome-wide profiling of DNA methylation (Infinium MethylationEPIC BeadChip) corrected for glial composition and DDR1 gene expression analysis in the occipital cortices of individuals with BD (n = 15) and healthy controls (n = 15) were conducted. Results:DDR1 5-methylcytosine levels were increased and directly associated with DDR1b mRNA expression in the brains of BD patients. We also observed that DDR1 was comethylated with a group of myelin genes. Conclusion:DDR1 is hypermethylated in BD brain tissue and is associated with isoform expression. Additionally, DDR1 comethylation with myelin genes supports the role of this receptor in myelination.

Keywords: bipolar disorder; discoidin domain receptor 1; gene expression; human brain; methylation; myelin genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Bipolar Disorder / diagnosis*
  • Bipolar Disorder / genetics*
  • Bipolar Disorder / metabolism
  • Brain / metabolism
  • Brain / physiopathology
  • Computational Biology / methods
  • CpG Islands
  • DNA Methylation*
  • Discoidin Domain Receptor 1 / genetics*
  • Disease Susceptibility
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Humans
  • Molecular Sequence Annotation
  • Myelin Sheath / genetics*
  • Myelin Sheath / metabolism
  • Protein Isoforms

Substances

  • Biomarkers
  • Protein Isoforms
  • DDR1 protein, human
  • Discoidin Domain Receptor 1