title: Associations with early-life socio-economic position in adult DNA methylation.
abstract: BACKGROUND
  Disadvantaged socio-economic position (SEP) in childhood is associated with increased adult mortality and morbidity. We aimed to establish whether childhood SEP was associated with differential methylation of adult DNA.
  
  
  METHODS
  Forty adult males from the 1958 British Birth Cohort Study were selected from SEP extremes in both early childhood and mid-adulthood. We performed genome-wide methylation analysis on blood DNA taken at 45 years using MeDIP (methylated DNA immunoprecipitation). We mapped in triplicate the methylation state of promoters of approximately 20,000 genes and 400 microRNAs. Probe methylation scores were averaged across triplicates and differential methylation between groups of individuals was determined. Differentially methylated promoter sites of selected genes were validated using pyrosequencing of bisulfite-converted DNA.
  
  
  RESULTS
  Variably methylated probes (9112 from n = 223,359 on the microarray) corresponded to 6176 gene promoters with at least one variable probe. Unsupervised hierarchical clustering of probes obtained from the 500 most variable promoters revealed a cluster enriched with high SEP individuals confirming that SEP differences contribute to overall epigenetic variation. Methylation levels for 1252 gene promoters were associated with childhood SEP vs 545 promoters for adulthood SEP. Functionally, associations with childhood SEP appear in promoters of genes enriched in key cell signalling pathways. The differentially methylated promoters associated with SEP cluster in megabase-sized regions of the genome.
  
  
  CONCLUSIONS
  Adult blood DNA methylation profiles show more associations with childhood SEP than adult SEP. Organization of these associations across the genome suggests a well-defined epigenetic pattern linked to early socio-economic environment.
authors.affiliation: Sackler Program for Epigenetics & Developmental Psychobiology, McGill University, Montreal, Quebec, Canada.
authors.forename: Nada
authors.initials: N
authors.lastname: Borghol
authors.forename: Matthew
authors.initials: M
authors.lastname: Suderman
authors.forename: Wendy
authors.initials: W
authors.lastname: McArdle
authors.forename: Ariane
authors.initials: A
authors.lastname: Racine
authors.forename: Michael
authors.initials: M
authors.lastname: Hallett
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.forename: Moshe
authors.initials: M
authors.lastname: Szyf
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002648:Child; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics; D012923:Social Class; D006113:United Kingdom; D055815:Young Adult