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Genes 2017, 8(5), 143; doi:10.3390/genes8050143

Variability of DNA Methylation within Schizophrenia Risk Loci across Subregions of Human Hippocampus

1
Program in Structural and Molecular Neuroscience, McLean Hospital, Belmont, MA 02478, USA
2
Department of Psychiatry, Harvard Medical School, Boston, MA 02478, USA
3
Program in Neuroscience, Harvard Medical School, Boston, MA 02478, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Dennis R. Grayson
Received: 7 March 2017 / Revised: 9 May 2017 / Accepted: 11 May 2017 / Published: 15 May 2017
(This article belongs to the Special Issue Role of Epigenetic Gene Regulation in Brain Function)
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Abstract

Identification of 108 genomic regions significantly associated with schizophrenia risk by the Psychiatric Genomics Consortium was a milestone for the field, and much work is now focused on determining the mechanism of risk associated with each locus. Within these regions, we investigated variability of DNA methylation, a low-level cellular phenotype closely linked to genotype, in two highly similar cellular populations sampled from the human hippocampus, to draw inferences about the elaboration of genotype to phenotype within these loci enriched for schizophrenia risk. DNA methylation was assessed with the Illumina HumanMethylation450 BeadArray in tissue laser-microdissected from the stratum oriens of subfield CA1 or CA2/3, regions having unique connectivity with intrinsic and extrinsic fiber systems within the hippocampus. Samples consisted of postmortem human hippocampus tissue from eight schizophrenia patients, eight bipolar disorder patients, and eight healthy control subjects. Within these genomic regions, we observed far greater difference in methylation patterns between circuit locations within subjects than in a single subregion between subjects across diagnostic groups, demonstrating the complexity of genotype to phenotype elaboration across the diverse circuitry of the human brain. View Full-Text
Keywords: DNA methylation; HumanMethylation450; schizophrenia; bipolar disorder; postmortem human brain; epigenetics; hippocampus DNA methylation; HumanMethylation450; schizophrenia; bipolar disorder; postmortem human brain; epigenetics; hippocampus
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Ruzicka, W.B.; Subburaju, S.; Benes, F.M. Variability of DNA Methylation within Schizophrenia Risk Loci across Subregions of Human Hippocampus. Genes 2017, 8, 143.

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