Most psychiatric disorders are not due to mutations in a single gene but rather involve cellular pathways under control of many genes and molecular signals. Recent studies point to the fact that complex epigenetic mechanisms regulating gene activity 'above'the genetic nucleotide sequence may be involved as well. The best understood mechanism of epigenetic modification is DNA methylation. In this genome-wide study we will examine the role of DNA methylation in schizophrenia susceptibility. Our study consists of a genome-wide discovery and replication phase to identify CpG loci in the human genome that are under epigenetic control and involved in disease susceptibility, followed by locus-specific validation in large schizophrenia cohorts. Our systematic approach for identifying candidate CpG loci involved in disease also includes study of general features of DNA methylation such as age, gender and genetic controls. The genome-wide effort with comparative analyses of multiple brain regions of patients and controls will provide a unique opportunity to establish what role DNA methylation plays in vulnerability to develop schizophrenia and perhaps other psychiatric traits.

Public Health Relevance

Biochemical modifications of DNA and chromosome structure provide heritable information that is not encoded in the DNA sequence itself, but is likely to play a role in disease susceptibility. We will screen the humangenome of schizophrenia patients and unaffected control subjects in order to identify these sites involved in disease. This will lead to a better understanding of the genetic basis of schizophrenia.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA028526-05
Application #
8521226
Study Section
Special Emphasis Panel (ZRG1-GGG-M (53))
Program Officer
Satterlee, John S
Project Start
2009-09-30
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
5
Fiscal Year
2013
Total Cost
$485,051
Indirect Cost
$170,083
Name
University of California Los Angeles
Department
None
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
van Eijk, Kristel R; de Jong, Simone; Strengman, Eric et al. (2015) Identification of schizophrenia-associated loci by combining DNA methylation and gene expression data from whole blood. Eur J Hum Genet 23:1106-10
Plongthongkum, Nongluk; van Eijk, Kristel R; de Jong, Simone et al. (2014) Characterization of genome-methylome interactions in 22 nuclear pedigrees. PLoS One 9:e99313
De Jong, Simone; Neeleman, Marjolein; Luykx, Jurjen J et al. (2014) Seasonal changes in gene expression represent cell-type composition in whole blood. Hum Mol Genet 23:2721-8