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Talens, R.P.; Boomsma, D.I.; Tobi, E.W.; Kremer, D.; Jukema, J.W.; Willemsen, G.; ... ; Heijmans, B.T. (2010)

Variation, patterns, and temporal stability of DNA methylation: considerations for epigenetic epidemiology

Article / Letter to editor
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 un-methylated 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...Show moreThe 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 un-methylated 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, R. P., Boomsma, D. I., Tobi, E. W., Kremer, D., Jukema, J. W., Willemsen, G., Putter, H., Slagboom, P. E., Heijmans, B. T. Variation, patterns, and temporal stability of DNA methylation: considerations for epigenetic epidemiology. FASEB J. 24, 3135-3144 (2010). www.fasebj.orgShow less
epigenome biobank human studies complex disease mass-spectrometry colorectal-cancer gene-expression epigenome locus twins association upstream imprints families
All authors
Talens, R.P.; Boomsma, D.I.; Tobi, E.W.; Kremer, D.; Jukema, J.W.; Willemsen, G.; Putter, H.; Slagboom, P.E.; Heijmans, B.T.
Date
2010-09-30
Journal
FASEB Journal
Volume
24
Issue
9
Pages
3135 - 3144
DOI
doi:10.1096/fj.09-150490