Systematic identification of genetic influences on methylation across the human life course

Gaunt, Tom R., Shihab, Hashem A., Hemani, Gibran, Min, Josine L., Woodward, Geoff, Lyttleton, Oliver, Zheng, Jie, Duggirala, Aparna, McArdle, Wendy L., Ho, Karen, Ring, Susan M., Evans, David M., Smith, George Davey and Relton, Caroline L. (2016) Systematic identification of genetic influences on methylation across the human life course. Genome Biology, 17 . doi:10.1186/s13059-016-0926-z

Author Gaunt, Tom R.
Shihab, Hashem A.
Hemani, Gibran
Min, Josine L.
Woodward, Geoff
Lyttleton, Oliver
Zheng, Jie
Duggirala, Aparna
McArdle, Wendy L.
Ho, Karen
Ring, Susan M.
Evans, David M.
Smith, George Davey
Relton, Caroline L.
Title Systematic identification of genetic influences on methylation across the human life course
Journal name Genome Biology   Check publisher's open access policy
ISSN 1465-6906
Publication date 2016-03-31
Year available 2016
Sub-type Article (original research)
DOI 10.1186/s13059-016-0926-z
Open Access Status DOI
Volume 17
Total pages 14
Place of publication London, United Kingdom
Publisher BioMed Central
Language eng
Formatted abstract
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.
Keyword Methylation quantitative trait loci
Genetic association
DNA methylation
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
UQ Diamantina Institute Publications
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