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Correspondence of DNA Methylation Between Blood and Brain Tissue and Its Application to Schizophrenia Research
Open accessAbstract
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.
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“several studies have reported that most DNA methylation markers detected in the peripheral tissues cannot accurately predict the DNA methylation status of the brain.87”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [87]
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“87 The latest advancements in array techniques enabled the use of hypothesis-free paradigms to examine the association of DNA methylation changes across the entire genome to study different phenotypes.”
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Metadata
- Authors
- Walton, E., Hass, J., Liu, J., Roffman, J. L., Bernardoni, F., Roessner, V., Kirsch, M., Schackert, G., Calhoun, V., & Ehrlich, S.
- Affiliations
- King's College London (GB)
- TransDeN Lab (DE)
- Mind Research Network (US)
- Massachusetts General Hospital (US)
- Center for Regenerative Therapies Dresden (DE)
- Technische Universität Dresden (DE)
- Corresponding author
- Ehrlich, Stefan
- ORCID
- Venue
- Schizophrenia Bulletin
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-06-08
- Volume
- 42
- Issue
- 2
- Pages
- 406-414
- ISSN
- 0586-7614 (ISSN-L)
- 1745-1701
- PMC
- PMC4753587
- OpenAlex
- W2256732880
- Cited by
- 286
- References
- 52
- Citations by year
- 2026: 16 · 2025: 19 · 2024: 14 · 2023: 21 · 2022: 21 · 2021: 39 · 2020: 31 · 2019: 31 · 2018: 36 · 2017: 37 · 2016: 16 · 2015: 5
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Schizophrenia Bulletin (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Explore Bristol Research (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Bristol Research (University of Bristol) (submittedVersion)
- Funders
- Eli Lilly and Company
- National Institutes of Health (5k08mh068540-05)
- National Institute of Mental Health (K08-MH068540)
- National Institute of General Medical Sciences (P20GM103472)
- National Institute of Biomedical Imaging and Bioengineering (R01EB000840, R01EB020407, R01EB005846, R01EB006841)
- National Center for Research Resources (U24RR021992, M01 RR025758-01, P41-RR-14075, U24RR021382, 1U24 RR021382A, UL1RR025758, P41RR014075)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- DNA methylation
- MeSH terms
- Brain, Humans, Schizophrenia, Biomarkers, CpG Islands, DNA Methylation, Epigenesis, Genetic
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