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

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.

Graphical abstract

Keywords::

• bipolar disorder
• discoidin domain receptor 1
• gene expression
• human brain
• methylation
• myelin genes

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2021-0006

Acknowledgments

We would like to thank the IISPV Biobank staff for their technical support and excellent work in the preparation and processing of the biological samples used in this work. The graphical abstract was created with BioRender.com.

Financial & competing interests disclosure

The study was supported by grants from the Brain and Behavior Research Foundation (‘2017 NARSAD Independent grant’ number 25811 to E Vilella) and from the Spanish Instituto de Salud Carlos III cofounded by FEDER (an CIBERSAM Intramural Project grant to E Vieta and PI15-00852 to E Vilella). E Vieta has received grants and served as consultant, advisor or CME speaker unrelated to this work for the following entities: AB-Biotics, Abbott, Allergan, Angelini, Dainippon Sumitomo Pharma, Ferrer, Gedeon Richter, Janssen, Lundbeck, Otsuka, Sage, Sanofi-Aventis, Sunovion and Takeda. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.