craig-earlylife-2022.pdf (4.45 MB)
Early life affects late-life health through determining DNA methylation across the lifespan: A twin study
journal contribution
posted on 2022-03-01, 00:00 authored by S Li, Z Ye, K A Mather, T L Nguyen, G S Dite, N J Armstrong, E M Wong, A Thalamuthu, G G Giles, Jeffrey CraigJeffrey Craig, R Saffery, M C Southey, Q Tan, P S Sachdev, J L HopperBackground: 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.
History
Journal
eBioMedicineVolume
77Article number
103927Pagination
1 - 15Publisher
ElsevierLocation
Amsterdam, The NetherlandsPublisher DOI
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eISSN
2352-3964Language
engPublication classification
C1 Refereed article in a scholarly journalUsage metrics
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DNA methylationTwin studyDOHaD hypothesisHeritabilityScience & TechnologyLife Sciences & BiomedicineMedicine, General & InternalMedicine, Research & ExperimentalGeneral & Internal MedicineResearch & Experimental MedicineBODY-MASS INDEXDEVELOPMENTAL ORIGINSSUBSET-QUANTILEBIRTH-WEIGHTDISEASEBLOODCANCERTISSUEWOMENNORMALIZATION
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