Testing two models describing how methylome-wide studies in blood are informative for psychiatric conditions

Abstract

Aim: As the primary relevant tissue (brain) for psychiatric disorders is commonly not available, we aimed to investigate whether blood can be used as a proxy in methylation studies on the basis of two models. In the ‘signature‘ model methylation–disease associations occur because a disease-causing factor affected methylation in the blood. In the ‘mirror-site‘ model the methylation status in the blood is correlated with the corresponding disease-causing site in the brain. Materials, methods & results: Methyl-binding domain enrichment and next-generation sequencing of the blood, cortex and hippocampus from four haloperidol-treated and ten untreated C57BL/6 mice revealed high levels of correlation in methylation across tissues. Despite the treatment inducing a large number of methylation changes, this correlation remains high. Conclusion: Our results show that, consistent with the signature model, factors that affect brain processes (i.e., haloperidol) leave biomarker signatures in the blood and, consistent with the mirror-site model, the methylation status of many sites in the blood mirror those in the brain.

KEYWORDS::

• antipsychotic
• DNA methylation
• methyl-CpG binding domain
• methylome-wide association study
• mirror-site model
• next-generation sequencing
• signature model

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/3dp-2022-0019

Financial & competing interests disclosure

This work was supported by a grant from the National Institute of Mental Health (RC2MH089996). 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.

Additional information

Funding

This work was supported by a grant from the National Institute of Mental Health (RC2MH089996). 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.