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

Yongsheng Li, Cynthia Camarillo, Juan Xu, Tania Bedard Arana, Yun Xiao, Zheng Zhao, Hong Chen, Mercedes Ramirez, Juan Zavala, Michael A. Escamilla, Regina Armas, Ricardo Mendoza, Alfonso Ontiveros, Humberto Nicolini, Alvaro Antonio Jerez Magaña, Lewis P. Rubin, Xia Li, Chun Xu

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

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) 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.

Original languageEnglish (US)
Article number201587
JournalBioMed Research International
Volume2015
DOIs
StatePublished - 2015
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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