title: Correspondence of DNA Methylation Between Blood and Brain Tissue and Its Application to Schizophrenia Research.
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.
authors.affiliation: Department of Child and Adolescent Psychiatry, Translational Developmental Neuroscience Section, Faculty of Medicine of the TU Dresden, Dresden, Germany; Department of Psychology, Institute of Psychology, Psychiatry and Neuroscience, King's College London, London, UK;
authors.forename: Esther
authors.initials: E
authors.lastname: Walton
authors.affiliation: Department of Child and Adolescent Psychiatry, Translational Developmental Neuroscience Section, Faculty of Medicine of the TU Dresden, Dresden, Germany; Institute of Tropical Medicine, Eberhard Karls University, Tübingen, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Hass
authors.affiliation: The Mind Research Network, Albuquerque, NM;
authors.forename: Jingyu
authors.initials: J
authors.lastname: Liu
authors.affiliation: MGH/MIT/HMS Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA; Department of Psychiatry, Massachusetts General Hospital, Boston, MA;
authors.forename: Joshua L
authors.initials: JL
authors.lastname: Roffman
authors.affiliation: Department of Child and Adolescent Psychiatry, Translational Developmental Neuroscience Section, Faculty of Medicine of the TU Dresden, Dresden, Germany;
authors.forename: Fabio
authors.initials: F
authors.lastname: Bernardoni
authors.affiliation: Department of Child and Adolescent Psychiatry, Translational Developmental Neuroscience Section, Faculty of Medicine of the TU Dresden, Dresden, Germany;
authors.forename: Veit
authors.initials: V
authors.lastname: Roessner
authors.affiliation: Department of Neurosurgery, Faculty of Medicine of the TU Dresden, Dresden, Germany; Center for Regenerative Therapies Dresden (CRTD), DFG Research Center and Cluster of Excellence at the TU Dresden, Dresden, Germany;
authors.forename: Matthias
authors.initials: M
authors.lastname: Kirsch
authors.affiliation: Department of Neurosurgery, Faculty of Medicine of the TU Dresden, Dresden, Germany;
authors.forename: Gabriele
authors.initials: G
authors.lastname: Schackert
authors.affiliation: The Mind Research Network, Albuquerque, NM; Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM.
authors.forename: Vince
authors.initials: V
authors.lastname: Calhoun
authors.affiliation: Department of Child and Adolescent Psychiatry, Translational Developmental Neuroscience Section, Faculty of Medicine of the TU Dresden, Dresden, Germany; MGH/MIT/HMS Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA; Department of Psychiatry, Massachusetts General Hospital, Boston, MA; transden.lab@uniklinikum-dresden.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Ehrlich
mesh_terms: D015415:Biomarkers / Q000097:blood / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D018899:CpG Islands; D019175:DNA Methylation / Q000502:physiology; D044127:Epigenesis, Genetic; D006801:Humans; D012559:Schizophrenia / Q000097:blood / Q000378:metabolism*
chemical_list: D015415:Biomarkers
keywords: DNA methylation; blood; brain; correlation; cross-tissue; schizophrenia