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dc.contributor.authorLi, Shuai
dc.contributor.authorYe, Zhoufeng
dc.contributor.authorMather, Karen A
dc.contributor.authorNguyen, Tuong L
dc.contributor.authorDite, Gillian S
dc.contributor.authorArmstrong, Nicola J
dc.contributor.authorWong, Ee Ming
dc.contributor.authorThalamuthu, Anbupalam
dc.contributor.authorGiles, Graham G
dc.contributor.authorCraig, Jeffrey M
dc.contributor.authorSaffery, Richard
dc.contributor.authorSouthey, Melissa C
dc.contributor.authorTan, Qihua
dc.contributor.authorSachdev, Perminder S
dc.contributor.authorHopper, John L
dc.date.accessioned2022-04-19T13:18:08Z
dc.date.available2022-04-19T13:18:08Z
dc.date.issued2022-03
dc.identifier.issn2352-3964
dc.identifier.other35301182
dc.identifier.otherPMC8927831
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/336180
dc.description.abstractBACKGROUND: 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.
dc.languageeng
dc.publisherElsevier BV
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourcenlmid: 101647039
dc.sourceessn: 2352-3964
dc.subjectDNA methylation
dc.subjectHeritability
dc.subjectTwin Study
dc.subjectDohad Hypothesis
dc.subjectHumans
dc.subjectDNA Methylation
dc.subjectLongevity
dc.subjectTwins, Dizygotic
dc.subjectTwins, Monozygotic
dc.subjectAdolescent
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectChild
dc.subjectChild, Preschool
dc.subjectInfant
dc.subjectInfant, Newborn
dc.subjectYoung Adult
dc.subjectEpigenomics
dc.titleEarly life affects late-life health through determining DNA methylation across the lifespan: A twin study.
dc.typeArticle
dc.date.updated2022-04-19T13:18:08Z
prism.publicationNameEBioMedicine
prism.volume77
dc.identifier.doi10.17863/CAM.83605
dcterms.dateAccepted2022-02-24
rioxxterms.versionofrecord10.1016/j.ebiom.2022.103927
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.contributor.orcidLi, Shuai [0000-0002-8696-8594]
dc.contributor.orcidNguyen, Tuong L [0000-0002-6597-8363]
dc.contributor.orcidArmstrong, Nicola J [0000-0002-4477-293X]
dc.contributor.orcidTan, Qihua [0000-0003-3194-0030]
dc.identifier.eissn2352-3964
cam.issuedOnline2022-03-14


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Attribution-NonCommercial-NoDerivatives 4.0 International
Except where otherwise noted, this item's licence is described as Attribution-NonCommercial-NoDerivatives 4.0 International