Correspondence of DNA Methylation Between Blood and Brain Tissue and Its Application to Schizophrenia Research

Esther Walton, Johanna Hass, Jingyu Liu, Joshua L Roffman, Fabio Bernardoni, Veit Roessner, Matthias Kirsch, Gabriele Schackert, Vince Calhoun, Stefan Ehrlich

Research output: Contribution to journalArticle (Academic Journal)

Abstract

Given the difficulty of procuring human brain tissue, a key question in molecular psychiatry concerns the extent to which epigenetic signatures measured in more accessible tissues such as blood can serve as a surrogate marker for the brain. Here, we aimed (1) to investigate the blood-brain correspondence of DNA methylation using a within-subject design and (2) to identify changes in DNA methylation of brain-related biological pathways in schizophrenia.We obtained paired blood and temporal lobe biopsy samples simultaneously from 12 epilepsy patients during neurosurgical treatment. Using the Infinium 450K methylation array we calculated similarity of blood and brain DNA methylation for each individual separately. We applied our findings by performing gene set enrichment analyses (GSEA) of peripheral blood DNA methylation data (Infinium 27K) of 111 schizophrenia patients and 122 healthy controls and included only Cytosine-phosphate-Guanine (CpG) sites that were significantly correlated across tissues.Only 7.9% of CpG sites showed a statistically significant, large correlation between blood and brain tissue, a proportion that although small was significantly greater than predicted by chance. GSEA analysis of schizophrenia data revealed altered methylation profiles in pathways related to precursor metabolites and signaling peptides.Our findings indicate that most DNA methylation markers in peripheral blood do not reliably predict brain DNA methylation status. However, a subset of peripheral data may proxy methylation status of brain tissue. Restricting the analysis to these markers can identify meaningful epigenetic differences in schizophrenia and potentially other brain disorders.

Original languageEnglish
Pages (from-to)406-14
Number of pages9
JournalSchizophrenia Bulletin
Volume42
Issue number2
DOIs
Publication statusPublished - Mar 2016

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    Cite this

    Walton, E., Hass, J., Liu, J., Roffman, J. L., Bernardoni, F., Roessner, V., Kirsch, M., Schackert, G., Calhoun, V., & Ehrlich, S. (2016). Correspondence of DNA Methylation Between Blood and Brain Tissue and Its Application to Schizophrenia Research. Schizophrenia Bulletin, 42(2), 406-14. https://doi.org/10.1093/schbul/sbv074