Systematic identification of genetic influences on methylation across the human life course. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Gaunt, Tom; Shihab, Hashem; Hemani, Gibran; Min, Josine; Woodward, Geoff; Lyttleton, Oliver; Zheng, Jie; Duggirala, Aparna; McArdle, Wendy; Ho, Karen; Ring, Susan; Evans, David; Davey Smith, George; Relton, Caroline
• Is Part Of: Genome biology. Volume 17:Issue 1(2016)
• Page Start: 1
• Page End: 14
• Publication Date: 2016-12
• Subjects: Methylation quantitative trait loci -- mQTL -- Cohort -- Genetic association -- DNA methylation; Genomes -- Periodicals; Biology -- Periodicals; Molecular biology -- Periodicals; 572.8633
• DOI: 10.1186/s13059-016-0926-z
• Languages: English
• ISSNs: 1474-760X

Abstract

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 thecis -acting genetic variation, a much larger component of genetic effects influencing methylation are acting intrans . However, only 7 % of discovered mQTL aretrans -effects, suggesting that thetrans 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.