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Lookup NU author(s): Professor Caroline Relton
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Background: The influence of genetic variation on complex diseases is potentially mediated through a range of highly dynamic epigenetic processes exhibiting temporal variation during development and later life. Here we present a catalogue of the genetic influences on DNA methylation (methylation quantitative trait loci (mQTL)) at five different life stages in human blood: children at birth, childhood, adolescence and their mothers during pregnancy and middle age.Results: We show that genetic effects on methylation are highly stable across the life course and that developmental change in the genetic contribution to variation in methylation occurs primarily through increases in environmental or stochastic effects. Though we map a large proportion of the cis-acting genetic variation, a much larger component of genetic effects influencing methylation are acting in trans. However, only 7 % of discovered mQTL are trans-effects, suggesting that the trans component is highly polygenic. Finally, we estimate the contribution of mQTL to variation in complex traits and infer that methylation may have a causal role consistent with an infinitesimal model in which many methylation sites each have a small influence, amounting to a large overall contribution.Conclusions: DNA methylation contains a significant heritable component that remains consistent across the lifespan. Our results suggest that the genetic component of methylation may have a causal role in complex traits. The database of mQTL presented here provide a rich resource for those interested in investigating the role of methylation in disease.
Author(s): Gaunt TR, Shihab HA, Hemani G, Min JL, Woodward G, Lyttleton O, Zheng J, Duggirala A, McArdle WL, Ho KR, Ring SM, Evans DM, Smith GD, Relton CL
Publication type: Article
Publication status: Published
Journal: Genome Biology
Year: 2016
Volume: 17
Online publication date: 31/03/2016
Acceptance date: 15/03/2016
Date deposited: 13/05/2016
ISSN (print): 1465-6906
ISSN (electronic): 1474-760X
Publisher: BioMed Central Ltd.
URL: http://dx.doi.org/10.1186/s13059-016-0926-z
DOI: 10.1186/s13059-016-0926-z
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