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

被引:234
作者
Talens, Rudolf P. [1 ]
Boomsma, Dorret I. [4 ]
Tobi, Elmar W. [1 ]
Kremer, Dennis [1 ]
Jukema, J. Wouter [2 ]
Willemsen, Gonneke [4 ]
Putter, Hein [3 ]
Slagboom, P. Eline [1 ,5 ]
Heijmans, Bastiaan T. [1 ,5 ]
机构
[1] Leiden Univ, Med Ctr, Dept Mol Epidemiol, NL-2300 RC Leiden, Netherlands
[2] Leiden Univ, Med Ctr, Dept Cardiol, NL-2300 RC Leiden, Netherlands
[3] Leiden Univ, Med Ctr, Dept Med Stat, NL-2300 RC Leiden, Netherlands
[4] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands
[5] Netherlands Consortium Healthy Ageing, Leiden, Netherlands
关键词
epigenome; biobank; human studies; complex disease; MASS-SPECTROMETRY; COLORECTAL-CANCER; GENE-EXPRESSION; EPIGENOME; LOCUS; TWINS; ASSOCIATION; UPSTREAM; IMPRINTS; FAMILIES;
D O I
10.1096/fj.09-150490
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 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.org
引用
收藏
页码:3135 / 3144
页数:10
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