Dataset Information

Early life affects late-life health through determining DNA methylation across the lifespan: A twin study.

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.

SUBMITTER: Li S

PROVIDER: S-EPMC8927831 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Early life affects late-life health through determining DNA methylation across the lifespan: A twin study.

Li Shuai S Ye Zhoufeng Z Mather Karen A KA Nguyen Tuong L TL Dite Gillian S GS Armstrong Nicola J NJ Wong Ee Ming EM Thalamuthu Anbupalam A Giles Graham G GG Craig Jeffrey M JM Saffery Richard R Southey Melissa C MC Tan Qihua Q Sachdev Perminder S PS Hopper John L JL

EBioMedicine 20220314

<h4>Background</h4>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.<h4>Methods</h4>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 t ...[more]

PMID: 35301182

Similar Datasets

Project description:BackgroundEarly life is a period of drastic epigenetic remodeling in which the epigenome is especially sensitive to extrinsic and intrinsic influence. However, the epigenome-wide dynamics of the DNA methylation changes that occur during this period have not been sufficiently characterized in longitudinal studies.MethodsTo this end, we studied the DNA methylation status of more than 750,000 CpG sites using Illumina MethylationEPIC arrays on 33 paired blood samples from 11 subjects at birth and at 5 and 10 years of age, then characterized the chromatin context associated with these loci by integrating our data with histone, chromatin-state and enhancer-element external datasets, and, finally, validated our results through bisulfite pyrosequencing in two independent longitudinal cohorts of 18 additional subjects.ResultsWe found abundant DNA methylation changes (110,726 CpG sites) during the first lustrum of life, while far fewer alterations were observed in the subsequent 5 years (460 CpG sites). However, our analysis revealed persistent DNA methylation changes at 240 CpG sites, indicating that there are genomic locations of considerable epigenetic change beyond immediate birth. The chromatin context of hypermethylation changes was associated with repressive genomic locations and genes with developmental and cell signaling functions, while hypomethylation changes were linked to enhancer regions and genes with immunological and mRNA and protein metabolism functions. Significantly, our results show that genes that suffer simultaneous hyper- and hypomethylation are functionally distinct from exclusively hyper- or hypomethylated genes, and that enhancer-associated methylation is different in hyper- and hypomethylation scenarios, with hypomethylation being more associated to epigenetic changes at blood tissue-specific enhancer elements.ConclusionsThese data show that epigenetic remodeling is dramatically reduced after the first 5 years of life. However, there are certain loci which continue to manifest DNA methylation changes, pointing towards a possible functionality beyond early development. Furthermore, our results deepen the understanding of the genomic context associated to hyper- or hypomethylation alterations during time, suggesting that hypomethylation of blood tissue-specific enhancer elements could be of importance in the establishment of functional states in blood tissue during early-life.

Dataset Information

Early life affects late-life health through determining DNA methylation across the lifespan: A twin study.

Background

Methods

Findings

Interpretation

Funding

Publications

Early life affects late-life health through determining DNA methylation across the lifespan: A twin study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets