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

Autor: Braun PR; Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, 52246, USA.; Interdisciplinary Graduate Program in Genetics, University of Iowa, Iowa City, IA, 52246, USA.; Department of Psychiatry and Behavioral Science, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA., Han S; Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, 52246, USA.; Interdisciplinary Graduate Program in Genetics, University of Iowa, Iowa City, IA, 52246, USA.; Department of Psychiatry and Behavioral Science, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA., Hing B; Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, 52246, USA., Nagahama Y; Department of Neurosurgery, University of Iowa Carver College of Medicine, Iowa City, IA, 52246, USA., Gaul LN; Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, 52246, USA., Heinzman JT; Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, 52246, USA., Grossbach AJ; Department of Neurosurgery, University of Iowa Carver College of Medicine, Iowa City, IA, 52246, USA.; Department of Neurological Surgery, Ohio State University, Columbus, OH, 43203, USA., Close L; Department of Neurosurgery, University of Iowa Carver College of Medicine, Iowa City, IA, 52246, USA., Dlouhy BJ; Department of Neurosurgery, University of Iowa Carver College of Medicine, Iowa City, IA, 52246, USA., Howard MA 3rd; Department of Neurosurgery, University of Iowa Carver College of Medicine, Iowa City, IA, 52246, USA., Kawasaki H; Department of Neurosurgery, University of Iowa Carver College of Medicine, Iowa City, IA, 52246, USA., Potash JB; Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, 52246, USA.; Interdisciplinary Graduate Program in Genetics, University of Iowa, Iowa City, IA, 52246, USA.; Department of Psychiatry and Behavioral Science, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA., Shinozaki G; Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, 52246, USA. gen-shinozaki@uiowa.edu.; Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, IA, 52246, USA. gen-shinozaki@uiowa.edu.; Interdisciplinary Graduate Program for Neuroscience, University of Iowa Carver College of Medicine, Iowa City, IA, 52246, USA. gen-shinozaki@uiowa.edu.
Jazyk: angličtina
Zdroj: Translational psychiatry [Transl Psychiatry] 2019 Jan 31; Vol. 9 (1), pp. 47. Date of Electronic Publication: 2019 Jan 31.
DOI: 10.1038/s41398-019-0376-y
Abstrakt: 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.
Databáze: MEDLINE