Epigenetic drift in the aging genome: a ten-year follow-up in an elderly twin cohort

Epigenetic drift in the aging genome: a ten-year follow-up in an elderly twin cohort
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DOI:
10.1093/ije/dyw132
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发表时间:
2016-08-01
影响因子:
7.7
通讯作者:
Christiansen, Lene
Christiansen, Lene
中科院分区:
医学1区
文献类型:
--
作者:
Tan, Qihua;Heijmans, Bastiaan T.;Christiansen, Lene

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Background: Current epigenetic studies on aging are dominated by the cross-sectional design that correlates subjects' ages or age groups with their measured epigenetic profiles. Such studies have been more aimed at age prediction or building up the epigenetic clock of age rather than focusing on the dynamic patterns in epigenetic changes during the aging process.Methods: We performed an epigenome-wide association study of intra-individual longitudinal changes in DNA methylation at CpG (cytosine-phosphate-guanine) sites measured in whole-blood samples of a cohort of 43 elderly twin pairs followed for 10 years (age at intake 73-82 years). Biological pathway analysis and survival analysis were also conducted on CpGs showing longitudinal change in their DNA-methylation levels. Classical twin models were fitted to each CpG site to estimate the genetic and environmental effects on DNA-methylation.Results: Our analysis identified 2284 CpG sites whose DNA-methylation levels changed longitudinally over the follow-up. Twin modelling revealed that the longitudinal change for 90% of these CpG sites was explained solely by individual unique environmental factors and only for 10% of these sites was it influenced by familial factors (genetic or shared environment). Over 60% of the identified CpG sites were replicated (same direction and replication P