Variation, patterns, and temporal stability of DNA methylation: considerations for epigenetic epidemiology.
The prospect of finding epigenetic risk factors for complex diseases would be greatly enhanced if DNA from existing biobanks, which is generally extracted from whole blood, could be used to perform epigenetic association studies. We characterized features of DNA methylation at 16 candidate loci, 8 of which were imprinted, in DNA samples from the Netherlands Twin Register biobank. Except for unmethylated or fully methylated sites, CpG methylation varied considerably in a sample of 30 unrelated individuals. This variation remained after accounting for the cellular heterogeneity of blood. Methylation of CpG sites was correlated within loci and, for 4 imprinted loci, across chromosomes. In 34 additional individuals, we investigated the DNA methylation of 8 representative loci in 2 longitudinal blood and 2 longitudinal buccal cell samples (follow-up 11-20 and 2-8 yr, respectively). Five of 8 loci were stable over time (rho>0.75) in both tissues, indicating that prospective epigenetic studies may be possible. For 4 loci, the DNA methylation in blood (mesoderm) correlated with that in the buccal cells (ectoderm) (rho>0.75). Our data suggest that epigenetic studies on complex diseases may be feasible for a proportion of genomic loci provided that they are carefully designed.
Talens
Rudolf P
RP
Department of Molecular Epidemiology, Leiden University Medical Center, Postal Zone S-05-P, PO box 9600, 2300RC, Leiden, The Nethelands.
Boomsma
Dorret I
DI
Tobi
Elmar W
EW
Kremer
Dennis
D
Jukema
J Wouter
JW
Willemsen
Gonneke
G
Putter
Hein
H
Slagboom
P Eline
PE
Heijmans
Bastiaan T
BT
D053302:Apolipoprotein C-I / Q000235:genetics; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics*; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics; D008297:Male; D017720:Molecular Epidemiology; D009426:Netherlands; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics; D017527:Receptor, IGF Type 2 / Q000235:genetics; D018433:Twin Studies as Topic
C505803:APOC1 protein, human; D053302:Apolipoprotein C-I; C485621:KCNQ1OT1 long non-coding RNA, human; D024642:Potassium Channels, Voltage-Gated; D017527:Receptor, IGF Type 2; D016753:Interleukin-10