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Genome-wide average DNA methylation is determined <i>in utero</i>
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, Anbupal Oxford University Press 2018 International journal of epidemiology Vol.47 No.3
<P><B>Abstract</B></P><P><B>Background</B></P><P>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.</P><P><B>Methods</B></P><P>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.</P><P><B>Results</B></P><P>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.</P><P><B>Conclusions</B></P><P>GWAM is determined <I>in utero</I> 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.</P>
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