Genome-Wide Dna Methylation Comparison Between Live Human Brain and Peripheral Tissues Within Individuals

• Published in: European neuropsychopharmacology 2017, Vol.27, p.S506-S506
• Main Authors: Braun, Patricia, Hafner, Marie, Nagahama, Yasunori, Hing, Benjamin, McKane, Melissa, Grossbach, Andrew, Howard, Matthew, Kawasaki, Hiroto, Potash, James, Shinozaki, Gen
• Format: Article
• Language: English
• ISSN: 0924-977X; 1873-7862
• DOI: 10.1016/j.euroneuro.2016.09.612

DNA methylation (DNAm) is a critical epigenetic mark impacting gene expression, and differential DNAm in the brain is associated with a number of psychiatric diseases. However, access to brain tissues to assess DNAm is essentially limited to post-mortem samples. The use of surrogate tissues, such as blood and saliva, has become common in identifying methylation changes associated with psychiatric disease. However, there is no literature showing direct association of DNAm between brain and peripheral tissues within individuals to support the validity of such surrogate tissues. In this study, we determined the extent to which these peripheral tissues can be used as surrogates for DNAm in the brain. DNA from blood, saliva, and live brain tissue samples from 12 treatment refractory epilepsy patients undergoing brain resection were collected. Genome-wide methylation was assessed with the Infinium HumanMethylation450 BeadChip array. Data were processed and analyzed with the R package RnBeads. Tissue relatedness was analyzed with Pearson correlation. Subsets of CpGs within different genomic regions, including promoter, genic, and intergenic regions, were evaluated for their degree of DNAm similarity. Blood and saliva showed a high degree of correlation for DNAm (r2=0.97), and saliva DNAm was revealed to be more similar to brain DNAm (r2=0.86) than was blood (r2=0.82; p