title: Genome-wide methylation changes in the brains of suicide completers.
abstract: OBJECTIVE
  Gene expression changes have been reported in the brains of suicide completers. More recently, differences in promoter DNA methylation between suicide completers and comparison subjects in specific genes have been associated with these changes in gene expression patterns, implicating DNA methylation alterations as a plausible component of the pathophysiology of suicide. The authors used a genome-wide approach to investigate the extent of DNA methylation alterations in the brains of suicide completers.
  
  
  METHODS
  Promoter DNA methylation was profiled using methylated DNA immunoprecipitation (MeDIP) followed by microarray hybridization in hippocampal tissue from 62 men (46 suicide completers and 16 comparison subjects). The correlation between promoter methylation and expression was investigated by comparing the MeDIP data with gene expression profiles generated through mRNA microarray. Methylation differences between groups were validated on neuronal and nonneuronal DNA fractions isolated by fluorescence-assisted cell sorting.
  
  
  RESULTS
  The authors identified 366 promoters that were differentially methylated in suicide completers relative to comparison subjects (273 hypermethylated and 93 hypomethylated). Overall, promoter methylation differences were inversely correlated with gene expression differences. Functional annotation analyses revealed an enrichment of differential methylation in the promoters of genes involved, among other functions, in cognitive processes. Validation was performed on the top genes from this category, and these differences were found to occur mainly in the neuronal cell fraction.
  
  
  CONCLUSIONS
  These results suggest broad reprogramming of promoter DNA methylation patterns in the hippocampus of suicide completers. This may help explain gene expression alterations associated with suicide and possibly behavioral changes increasing suicide risk.
authors.affiliation: McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal, USA.
authors.forename: Benoit
authors.initials: B
authors.lastname: Labonté
authors.forename: Matt
authors.initials: M
authors.lastname: Suderman
authors.forename: Gilles
authors.initials: G
authors.lastname: Maussion
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Lopez
authors.forename: Luis
authors.initials: L
authors.lastname: Navarro-Sánchez
authors.forename: Volodymyr
authors.initials: V
authors.lastname: Yerko
authors.forename: Naguib
authors.initials: N
authors.lastname: Mechawar
authors.forename: Moshe
authors.initials: M
authors.lastname: Szyf
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Meaney
authors.forename: Gustavo
authors.initials: G
authors.lastname: Turecki
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D019175:DNA Methylation / Q000235:genetics*; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D015894:Genome, Human / Q000235:genetics*; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008297:Male; D009474:Neurons / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013405:Suicide