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BioMed Research International
Volume 2015 (2015), Article ID 201587, 15 pages
Research Article

Genome-Wide Methylome Analyses Reveal Novel Epigenetic Regulation Patterns in Schizophrenia and Bipolar Disorder

1College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150086, China
2Center of Excellence in Neuroscience and Department of Psychiatry, Paul L. Foster School of Medicine, Texas Tech University Health Science Center, El Paso, TX 79905, USA
3Department of Pediatrics, Paul L. Foster School of Medicine, Texas Tech University Health Science Center, El Paso, TX 79905, USA
4Department of Psychiatry, University of California at San Francisco, San Francisco, CA 94103, USA
5Los Angeles Biomedical Research Center at Harbor, University of California Los Angeles Medical Center, Torrance, CA 90502, USA
6Instituto de Informacion de Investigacion en Salud Mental, 64710 Monterrey, NL, Mexico
7Medical and Family Research Group, Carracci S.C., 03740 Mexico City, DF, Mexico
8Centro Internacional de Trastornos Afectivos y de la Conducta Adictiva (CITACA), 01010 Guatemala City, Guatemala

Received 23 April 2014; Revised 16 September 2014; Accepted 18 September 2014

Academic Editor: Daniela Parolaro

Copyright © 2015 Yongsheng Li et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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) promoter CGIs hypermethylation with gene repression and (2) CGI 3′-shore hypomethylation with increased gene expression. Finally, we constructed a specific methylation analysis platform that facilitates viewing and comparing aberrant genome methylation in human neuropsychiatric disorders.