title: Intra-individual change over time in DNA methylation with familial clustering.
abstract: BACKGROUND
  Changes over time in epigenetic marks, which are modifications of DNA such as by DNA methylation, may help explain the late onset of common human diseases. However, changes in methylation or other epigenetic marks over time in a given individual have not yet been investigated.
  
  
  OBJECTIVE
  To determine whether there are longitudinal changes in global DNA methylation in individuals and to evaluate whether methylation maintenance demonstrates familial clustering.
  
  
  METHODS
  We measured global DNA methylation by luminometric methylation assay, a quantitative measurement of genome-wide DNA methylation, on DNA sampled at 2 visits on average 11 years apart in 111 individuals from an Icelandic cohort (1991 and 2002-2005) and on average 16 years apart in 126 individuals from a Utah sample (1982-1985 and 1997-2005).
  
  
  METHODS
  Global methylation changes over time.
  
  
  RESULTS
  Twenty-nine percent of Icelandic individuals showed greater than 10% methylation change over time (P < .001). The family-based Utah sample also showed intra-individual changes over time, and further demonstrated familial clustering of methylation change (P = .003). The family showing the greatest global methylation loss also demonstrated the greatest loss of gene-specific methylation by a separate methylation assay.
  
  
  CONCLUSIONS
  These data indicate that methylation changes over time and suggest that methylation maintenance may be under genetic control.
authors.affiliation: Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Hans T
authors.initials: HT
authors.lastname: Bjornsson
authors.forename: Martin I
authors.initials: MI
authors.lastname: Sigurdsson
authors.forename: M Daniele
authors.initials: MD
authors.lastname: Fallin
authors.forename: Rafael A
authors.initials: RA
authors.lastname: Irizarry
authors.forename: Thor
authors.initials: T
authors.lastname: Aspelund
authors.forename: Hengmi
authors.initials: H
authors.lastname: Cui
authors.forename: Wenqiang
authors.initials: W
authors.lastname: Yu
authors.forename: Michael A
authors.initials: MA
authors.lastname: Rongione
authors.forename: Tomas J
authors.initials: TJ
authors.lastname: Ekström
authors.forename: Tamara B
authors.initials: TB
authors.lastname: Harris
authors.forename: Lenore J
authors.initials: LJ
authors.lastname: Launer
authors.forename: Gudny
authors.initials: G
authors.lastname: Eiriksdottir
authors.forename: Mark F
authors.initials: MF
authors.lastname: Leppert
authors.forename: Carmen
authors.initials: C
authors.lastname: Sapienza
authors.forename: Vilmundur
authors.initials: V
authors.lastname: Gudnason
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Feinberg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D007055:Iceland; D008137:Longitudinal Studies; D008163:Luminescent Measurements; D008297:Male; D010375:Pedigree; D013997:Time Factors; D014589:Utah