title: Childhood abuse is associated with methylation of multiple loci in adult DNA.
abstract: BACKGROUND
  Childhood abuse is associated with increased adult disease risk, suggesting that processes acting over the long-term, such as epigenetic regulation of gene activity, may be involved. DNA methylation is a critical mechanism in epigenetic regulation. We aimed to establish whether childhood abuse was associated with adult DNA methylation profiles.
  
  
  METHODS
  In 40 males from the 1958 British Birth Cohort we compared genome-wide promoter DNA methylation in blood taken at 45y for those with, versus those without, childhood abuse (n = 12 vs 28). We analysed the promoter methylation of over 20,000 genes and 489 microRNAs, using MeDIP (methylated DNA immunoprecipitation) in triplicate.
  
  
  RESULTS
  We found 997 differentially methylated gene promoters (311 hypermethylated and 686 hypomethylated) in association with childhood abuse and these promoters were enriched for genes involved in key cell signaling pathways related to transcriptional regulation and development. Using bisulfite-pyrosequencing, abuse-associated methylation (MeDIP) at the metalloproteinase gene, PM20D1, was validated and then replicated in an additional 27 males. Abuse-associated methylation was observed in 39 microRNAs; in 6 of these, the hypermethylated state was consistent with the hypomethylation of their downstream gene targets. Although distributed across the genome, the differentially methylated promoters associated with child abuse clustered in genome regions of at least one megabase. The observations for child abuse showed little overlap with methylation patterns associated with socioeconomic position.
  
  
  CONCLUSIONS
  Our observed genome-wide methylation profiles in adult DNA associated with childhood abuse justify the further exploration of epigenetic regulation as a mediating mechanism for long-term health outcomes.
authors.forename: Matthew
authors.initials: M
authors.lastname: Suderman
authors.forename: Nada
authors.initials: N
authors.lastname: Borghol
authors.forename: Jane J
authors.initials: JJ
authors.lastname: Pappas
authors.forename: Snehal M
authors.initials: SM
authors.lastname: Pinto Pereira
authors.forename: Marcus
authors.initials: M
authors.lastname: Pembrey
authors.forename: Clyde
authors.initials: C
authors.lastname: Hertzman
authors.forename: Chris
authors.initials: C
authors.lastname: Power
authors.affiliation: Sackler Program for Epigenetics & Developmental Psychobiology, McGill University, 3655 Promenade Sir William Osler, Montreal H3G 1Y6, QC, Canada. moshe.szyf@mcgill.ca.
authors.forename: Moshe
authors.initials: M
authors.lastname: Szyf
mesh_terms: D000328:Adult; D020029:Base Pairing / Q000235:genetics; D002648:Child; D002649:Child Abuse; D016000:Cluster Analysis; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D056726:Genetic Association Studies; D056426:Genetic Loci; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D015203:Reproducibility of Results; D012959:Socioeconomic Factors; D060449:Wnt Signaling Pathway / Q000235:genetics
chemical_list: D035683:MicroRNAs