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Genome-wide average DNA methylation is determined in utero

Li, Shuai, Wong, Ee Ming, Dugué, Pierre-Antoine, McRae, Allan F, Kim, Eunae, Joo, Ji-Hoon Eric, Nguyen, Tuong L, Stone, Jennifer, Dite, Gillian S, Armstrong, Nicola J, Mather, Karen A, Thalamuthu, Anbupalam, Wright, Margaret J, Ames, David, Milne, Roger L, Craig, Jeffrey M, Saffery, Richard, Montgomery, Grant W, Song, Yun-Mi, Sung, Joohon, Spector, Timothy D, Sachdev, Perminder S, Giles, Graham G, Southey, Melissa C and Hopper, John L 2018, Genome-wide average DNA methylation is determined in utero, International journal of epidemiology, vol. 47, no. 3, pp. 908-916, doi: 10.1093/ije/dyy028.

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Title Genome-wide average DNA methylation is determined in utero
Author(s) Li, Shuai
Wong, Ee Ming
Dugué, Pierre-Antoine
McRae, Allan F
Kim, Eunae
Joo, Ji-Hoon Eric
Nguyen, Tuong L
Stone, Jennifer
Dite, Gillian S
Armstrong, Nicola J
Mather, Karen A
Thalamuthu, Anbupalam
Wright, Margaret J
Ames, David
Milne, Roger L
Craig, Jeffrey MORCID iD for Craig, Jeffrey M orcid.org/0000-0003-3979-7849
Saffery, Richard
Montgomery, Grant W
Song, Yun-Mi
Sung, Joohon
Spector, Timothy D
Sachdev, Perminder S
Giles, Graham G
Southey, Melissa C
Hopper, John L
Journal name International journal of epidemiology
Volume number 47
Issue number 3
Start page 908
End page 916
Total pages 9
Publisher Oxford University Press
Place of publication Oxford, Eng.
Publication date 2018-06
ISSN 0300-5771
1464-3685
Keyword(s) epigenomics
DNA methylation
twin study
Summary Background: Investigating the genetic and environmental causes of variation in genome-wide average DNA methylation (GWAM), a global methylation measure from the HumanMethylation450 array, might give a better understanding of genetic and environmental influences on methylation.

Methods: We measured GWAM for 2299 individuals aged 0 to 90 years from seven twin and/or family studies. We estimated familial correlations, modelled correlations with cohabitation history and fitted variance components models for GWAM.

Results: The correlation in GWAM for twin pairs was ∼0.8 at birth, decreased with age during adolescence and was constant at ∼0.4 throughout adulthood, with no evidence that twin pair correlations differed by zygosity. Non-twin first-degree relatives were correlated, from 0.17 [95% confidence interval (CI): 0.05-0.30] to 0.28 (95% CI: 0.08-0.48), except for middle-aged siblings (0.01, 95% CI: -0.10-0.12), and the correlation increased with time living together and decreased with time living apart. Spouse pairs were correlated in all studies, from 0.23 (95% CI: 0.3-0.43) to 0.31 (95% CI: 0.05-0.52), and the correlation increased with time living together. The variance explained by environmental factors shared by twins alone was 90% (95% CI: 74-95%) at birth, decreased in early life and plateaued at 28% (95% CI: 17-39%) in middle age and beyond. There was a cohabitation-related environmental component of variance.

Conclusions: GWAM is determined in utero by prenatal environmental factors, the effects of which persist throughout life. The variation of GWAM is also influenced by environmental factors shared by family members, as well as by individual-specific environmental factors.
Language eng
DOI 10.1093/ije/dyy028
Field of Research 0104 Statistics
1117 Public Health And Health Services
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2018, The Authors
Free to Read? Yes
Use Rights Creative Commons Attribution non-commercial licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30109593

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
Open Access Collection
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.