RT Journal Article
SR Electronic
T1 Epigenetic influences on aging: a longitudinal genome-wide methylation study in old Swedish twins
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 226266
DO 10.1101/226266
A1 Yunzhang Wang
A1 Robert Karlsson
A1 Erik Lampa
A1 Qian Zhang
A1 Åsa K. Hedman
A1 Malin Almgren
A1 Catarina Almqvist
A1 Allan F. McRae
A1 Riccardo Marioni
A1 Erik Ingelsson
A1 Peter M. Visscher
A1 Ian J. Deary
A1 Lars Lind
A1 Tiffany Morris
A1 Stephan Beck
A1 Nancy L. Pedersen
A1 Sara Hägg
YR 2017
UL http://biorxiv.org/content/early/2017/11/29/226266.abstract
AB Age-related changes in DNA methylation have been observed in many cross-sectional studies, but longitudinal evidence is still very limited. Here, we aimed to characterize longitudinal age-related methylation patterns (Illumina HumanMethylation450 array) using 1011 blood samples collected from 385 old Swedish twins (mean age of 69 at baseline) up to five times over 20 years. We identified 1316 age-associated methylation sites (p<1.3×10−7) using a longitudinal epigenome-wide association study design. We measured how estimated cellular compositions changed with age and how much they confounded the age effect. We validated the results in two independent longitudinal cohorts, where 118 CpGs were replicated in PIVUS (p<3.9×10−5) and 594 were replicated in LBC (p<5.1×10−5). Functional annotation of age-associated CpGs showed enrichment in CCCTC-binding factor (CTCF) and other unannotated transcription factor binding sites. We further investigated genetic influences on methylation (methylation quantitative trait loci) and found no interaction between age and genetic effects in the 1316 age-associated CpGs. Moreover, in the same CpGs, methylation differences within twin pairs increased over time, where monozygotic twins had smaller intra-pair differences than dizygotic twins. We show that age-related methylation changes persist in a longitudinal perspective, and are fairly stable across cohorts. Moreover, the changes are under genetic influence, although this effect is independent of age. In addition, inter-individual methylation variations increase over time, especially in age-associated CpGs, indicating the increase of environmental contributions on DNA methylation with age.