title: Adult global DNA methylation in relation to pre-natal nutrition.
abstract: BACKGROUND
  Exposure to a pre-natal famine environment has been associated with a persistent decrease in DNA methylation of the IGF2 gene, although study findings on other loci have been highly variable. There have been no studies to date of the relation between pre-natal famine and overall global DNA methylation in adulthood.
  
  
  METHODS
  Our study population includes 350 births with pre-natal exposure to the Dutch famine of 1944-45 selected from three birth clinics, 290 births from these clinics born before or after the famine as unexposed time controls and 307 same-sex siblings of either birth group as unexposed family controls. All study subjects were interviewed and underwent a medical examination at a mean age of 58 years when blood samples were also collected. As measures of genomic DNA methylation, we analysed two repetitive elements, LINE-1 (long interspersed nucleotide element 1) and Sat2 (Satellite 2 DNA sequence) by pyrosequencing and MethyLight, respectively, and overall genomic DNA methylation using the Luminometric methylation assay (LUMA).
  
  
  RESULTS
  Mean DNA methylation by LUMA was 75.2% [standard deviation (SD) 4.7], by LINE-1 was 77.1% (SD 2.5) and by Sat2 was 122.2 (SD 56.2). Pre-natal famine exposure was associated with negligible changes in all three assays {LUMA: -0.16% [95% confidence interval (95% CI) -0.49 to 0.81], P = 0.63; LINE-1: -0.05 % (95% CI -0.33 to 0.22), P = 0.70; and Sat2: -0.51% (95% CI -7.38 to 6.36), P = 0.88} relative to unexposed controls, adjusting for age at examination and within family clustering.
  
  
  CONCLUSIONS
  Our results show no relation between overall global DNA methylation in adults and pre-natal famine exposure. Further work should focus on selected regions in the genome that may be differentially methylated in response to changes in early life exposures and predict adult health outcomes.
authors.affiliation: Department of Epidemiology, Mailman School of Public Health, Columbia University Medical Center, New York, NY, USA. lumey@columbia.edu
authors.forename: L H
authors.initials: LH
authors.lastname: Lumey
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Terry
authors.forename: Lissette
authors.initials: L
authors.lastname: Delgado-Cruzata
authors.forename: Yuyan
authors.initials: Y
authors.lastname: Liao
authors.forename: Qiao
authors.initials: Q
authors.lastname: Wang
authors.forename: Ezra
authors.initials: E
authors.lastname: Susser
authors.forename: Ian
authors.initials: I
authors.lastname: McKeague
authors.forename: Regina M
authors.initials: RM
authors.lastname: Santella
mesh_terms: D016022:Case-Control Studies; D019175:DNA Methylation; D004276:DNA, Satellite / Q000235:genetics; D005260:Female; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics*; D039401:Prenatal Nutritional Physiological Phenomena; D035781:Siblings; D013217:Starvation / Q000150:complications*
chemical_list: D004276:DNA, Satellite