Intra-individual change over time in DNA methylation with familial clustering.
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.
Bjornsson
Hans T
HT
Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
Sigurdsson
Martin I
MI
Fallin
M Daniele
MD
Irizarry
Rafael A
RA
Aspelund
Thor
T
Cui
Hengmi
H
Yu
Wenqiang
W
Rongione
Michael A
MA
Ekström
Tomas J
TJ
Harris
Tamara B
TB
Launer
Lenore J
LJ
Eiriksdottir
Gudny
G
Leppert
Mark F
MF
Sapienza
Carmen
C
Gudnason
Vilmundur
V
Feinberg
Andrew P
AP
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