Early life affects late-life health through determining DNA methylation across the lifespan: A twin study.
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Authors
Ye, Zhoufeng
Mather, Karen A
Dite, Gillian S
Wong, Ee Ming
Thalamuthu, Anbupalam
Giles, Graham G
Craig, Jeffrey M
Saffery, Richard
Southey, Melissa C
Sachdev, Perminder S
Hopper, John L
Publication Date
2022-03Journal Title
EBioMedicine
ISSN
2352-3964
Publisher
Elsevier BV
Volume
77
Language
eng
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Li, S., Ye, Z., Mather, K. A., Nguyen, T. L., Dite, G. S., Armstrong, N. J., Wong, E. M., et al. (2022). Early life affects late-life health through determining DNA methylation across the lifespan: A twin study.. EBioMedicine, 77 https://doi.org/10.1016/j.ebiom.2022.103927
Abstract
BACKGROUND: Previous findings for the genetic and environmental contributions to DNA methylation variation were for limited age ranges only. We investigated the lifespan contributions and their implications for human health for the first time. METHODS: 1,720 monozygotic twin (MZ) pairs and 1,107 dizygotic twin (DZ) pairs aged 0-92 years were included. Familial correlations (i.e., correlations between twins) for 353,681 methylation sites were estimated and modelled as a function of twin pair cohabitation history. FINDINGS: The methylome average familial correlation was around zero at birth (MZ pair: -0.01; DZ pair: -0.04), increased with the time of twins living together during childhood at rates of 0.16 (95%CI: 0.12-0.20) for MZ pairs and 0.13 (95%CI: 0.07-0.20) for DZ pairs per decade, and decreased with the time of living apart during adulthood at rates of 0.026 (95%CI: 0.019-0.033) for MZ pairs and 0.027 (95%CI: 0.011-0.043) for DZ pairs per decade. Neither the increasing nor decreasing rate differed by zygosity (both P>0.1), consistent with cohabitation environment shared by twins, rather than genetic factors, influencing the methylation familial correlation changes. Familial correlations for 6.6% (23,386/353,681) sites changed with twin pair cohabitation history. These sites were enriched for high heritability, proximal promoters, and epigenetic/genetic associations with various early-life factors and late-life health conditions. INTERPRETATION: Early life strongly influences DNA methylation variation across the lifespan, and the effects are stronger for heritable sites and sites biologically relevant to the regulation of gene expression. Early life could affect late-life health through influencing DNA methylation. FUNDING: Victorian Cancer Agency, Cancer Australia, Cure Cancer Foundation.
Keywords
DNA methylation, Heritability, Twin Study, Dohad Hypothesis, Humans, DNA Methylation, Longevity, Twins, Dizygotic, Twins, Monozygotic, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Child, Child, Preschool, Infant, Infant, Newborn, Young Adult, Epigenomics
Identifiers
35301182, PMC8927831
External DOI: https://doi.org/10.1016/j.ebiom.2022.103927
This record's URL: https://www.repository.cam.ac.uk/handle/1810/336180
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International
Licence URL: https://creativecommons.org/licenses/by-nc-nd/4.0/
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