Genome-wide DNA methylation comparison between live human brain and peripheral tissues within individuals

Patricia R Braun; Shizhong Han; Benjamin Hing; Yasunori Nagahama; Lindsey N Gaul; Jonathan T Heinzman; Andrew J Grossbach; Liesl Close; Brian J Dlouhy; Matthew A Howard III; Hiroto Kawasaki; James B Potash; Gen Shinozaki

doi:10.1038/s41398-019-0376-y

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Genome-wide DNA methylation comparison between live human brain and peripheral tissues within individuals

Journal article

Open access

Peer reviewed

Genome-wide DNA methylation comparison between live human brain and peripheral tissues within individuals

Patricia R Braun, Shizhong Han, Benjamin Hing, Yasunori Nagahama, Lindsey N Gaul, Jonathan T Heinzman, Andrew J Grossbach, Liesl Close, Brian J Dlouhy, Matthew A Howard III, …

Translational psychiatry, Vol.9(1), pp.47-47

01/31/2019

DOI: 10.1038/s41398-019-0376-y

PMCID: PMC6355837

PMID: 30705257

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Abstract

Differential DNA methylation in the brain is associated with many psychiatric diseases, but access to brain tissues is essentially limited to postmortem samples. The use of surrogate tissues has become common in identifying methylation changes associated with psychiatric disease. In this study, we determined the extent to which peripheral tissues can be used as surrogates for DNA methylation in the brain. Blood, saliva, buccal, and live brain tissue samples from 27 patients with medically intractable epilepsy undergoing brain resection were collected (age range 5-61 years). Genome-wide methylation was assessed with the Infinium HumanMethylation450 (n = 12) and HumanMethylationEPIC BeadChip arrays (n = 21). For the EPIC methylation data averaged for each CpG across subjects, the saliva-brain correlation (r = 0.90) was higher than that for blood-brain (r = 0.86) and buccal-brain (r = 0.85) comparisons. However, within individual CpGs, blood had the highest proportion of CpGs correlated to brain at nominally significant levels (20.8%), as compared to buccal tissue (17.4%) and saliva (15.1%). For each CpG and each gene, levels of brain-peripheral tissue correlation varied widely. This indicates that to determine the most useful surrogate tissue for representing brain DNA methylation, the patterns specific to the genomic region of interest must be considered. To assist in that objective, we have developed a website, IMAGE-CpG, that allows researchers to interrogate DNA methylation levels and degree of cross-tissue correlation in user-defined locations across the genome.

Genome-Wide Association Study

Epigenesis, Genetic

Humans

Middle Aged

Child, Preschool

Male

Brain - metabolism

Young Adult

Mental Disorders - genetics

DNA Methylation

Saliva - metabolism

Adolescent

CpG Islands

Adult

Female

Child

Details

Title: Subtitle: Genome-wide DNA methylation comparison between live human brain and peripheral tissues within individuals
Creators: Patricia R Braun - Department of Psychiatry and Behavioral Science, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
Shizhong Han - Department of Psychiatry and Behavioral Science, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
Benjamin Hing - Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, 52246, USA
Yasunori Nagahama - Department of Neurosurgery, University of Iowa Carver College of Medicine, Iowa City, IA, 52246, USA
Lindsey N Gaul - Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, 52246, USA
Jonathan T Heinzman - Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, 52246, USA
Andrew J Grossbach - Department of Neurological Surgery, Ohio State University, Columbus, OH, 43203, USA
Liesl Close - Department of Neurosurgery, University of Iowa Carver College of Medicine, Iowa City, IA, 52246, USA
Brian J Dlouhy - Department of Neurosurgery, University of Iowa Carver College of Medicine, Iowa City, IA, 52246, USA
Matthew A Howard III - Department of Neurosurgery, University of Iowa Carver College of Medicine, Iowa City, IA, 52246, USA
Hiroto Kawasaki - Department of Neurosurgery, University of Iowa Carver College of Medicine, Iowa City, IA, 52246, USA
James B Potash - Department of Psychiatry and Behavioral Science, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
Gen Shinozaki - Interdisciplinary Graduate Program for Neuroscience, University of Iowa Carver College of Medicine, Iowa City, IA, 52246, USA. gen-shinozaki@uiowa.edu
Resource Type: Journal article
Publication Details: Translational psychiatry, Vol.9(1), pp.47-47
DOI: 10.1038/s41398-019-0376-y
PMID: 30705257
PMCID: PMC6355837
NLM abbreviation: Transl Psychiatry
ISSN: 2158-3188
eISSN: 2158-3188
Publisher: United States
Grant note: S10 OD016199 / NIH HHS T32 GM008629 / NIGMS NIH HHS T35 HL007485 / NHLBI NIH HHS K23 MH107654 / NIMH NIH HHS
Language: English
Date published: 01/31/2019
Academic Unit: Neurology; Molecular Physiology and Biophysics; Psychiatry; Iowa Neuroscience Institute; Anesthesia; Neurosurgery; Otolaryngology
Record Identifier: 9984004181702771

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