Genome-wide methylome analyses reveal novel epigenetic regulation patterns in schizophrenia and bipolar disorder

BioMed Research International
Yongsheng LiChun Xu

Abstract

Schizophrenia (SZ) and bipolar disorder (BP) are complex genetic disorders. Their appearance is also likely informed by as yet only partially described epigenetic contributions. Using a sequencing-based method for genome-wide analysis, we quantitatively compared the blood DNA methylation landscapes in SZ and BP subjects to control, both in an understudied population, Hispanics along the US-Mexico border. Remarkably, we identified thousands of differentially methylated regions for SZ and BP preferentially located in promoters 3'-UTRs and 5'-UTRs of genes. Distinct patterns of aberrant methylation of promoter sequences were located surrounding transcription start sites. In these instances, aberrant methylation occurred in CpG islands (CGIs) as well as in flanking regions as well as in CGI sparse promoters. Pathway analysis of genes displaying these distinct aberrant promoter methylation patterns showed enhancement of epigenetic changes in numerous genes previously related to psychiatric disorders and neurodevelopment. Integration of gene expression data further suggests that in SZ aberrant promoter methylation is significantly associated with altered gene transcription. In particular, we found significant associations between (1)...Continue Reading

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Citations

Jan 23, 2016·Clinical Epigenetics·Rosie May WalkerKathryn Louise Evans
Nov 27, 2015·Molecular and Cellular Neurosciences·K Sue O'Shea, Melvin G McInnis
May 21, 2015·The International Journal of Neuropsychopharmacology·Lien WangOlivier Civelli
Mar 6, 2015·Reproductive Biomedicine Online·John B Appleby, Sarah Franklin
Jun 23, 2016·Neuroscience and Biobehavioral Reviews·Gabriel R FriesJoao Quevedo

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Datasets Mentioned

BETA
SRP046293

Methods Mentioned

BETA
immunoprecipitation
MeDIP-Seq
PCR
RNA-Seq
methylation

Software Mentioned

MeDIP
IlluminaHiseq
Gene Set Analysis Toolkit
GSEA
PDMeth
SOAP2
epitools R - package
Gene Set Enrichment Analysis ( GSEA )

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