Deakin University
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Genome-wide average DNA methylation is determined in utero

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journal contribution
posted on 2018-06-01, 00:00 authored by Shuai Li, Ee Ming Wong, Pierre-Antoine Dugué, Allan F McRae, Eunae Kim, Ji-Hoon Eric Joo, Tuong L Nguyen, Jennifer Stone, Gillian S Dite, Nicola J Armstrong, Karen A Mather, Anbupalam Thalamuthu, Margaret J Wright, David Ames, Roger L Milne, Jeffrey CraigJeffrey Craig, Richard Saffery, Grant W Montgomery, Yun-Mi Song, Joohon Sung, Timothy D Spector, Perminder S Sachdev, Graham G Giles, Melissa C Southey, John L Hopper
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.



International journal of epidemiology






908 - 916


Oxford University Press


Oxford, Eng.







Publication classification

C1 Refereed article in a scholarly journal

Copyright notice

2018, The Authors