Contribution of genetic variation to transgenerational inheritance of DNA methylation

McRae, Allan F., Powell, Joseph E., Henders, Anjali K., Bowdler, Lisa, Hemani, Gibran, Shah, Sonia, Painter, Jodie N., Martin, Nicholas G., Visscher, Peter M. and Montgomery, Grant W. (2014) Contribution of genetic variation to transgenerational inheritance of DNA methylation. Genome Biology, 15 5: 1-10. doi:10.1186/gb-2014-15-5-r73

Author McRae, Allan F.
Powell, Joseph E.
Henders, Anjali K.
Bowdler, Lisa
Hemani, Gibran
Shah, Sonia
Painter, Jodie N.
Martin, Nicholas G.
Visscher, Peter M.
Montgomery, Grant W.
Title Contribution of genetic variation to transgenerational inheritance of DNA methylation
Journal name Genome Biology   Check publisher's open access policy
ISSN 1474-760X
Publication date 2014-05-29
Year available 2014
Sub-type Article (original research)
DOI 10.1186/gb-2014-15-5-r73
Open Access Status DOI
Volume 15
Issue 5
Start page 1
End page 10
Total pages 10
Place of publication London, United Kingdom
Publisher BioMed Central
Language eng
Formatted abstract
Background: Despite the important role DNA methylation plays in transcriptional regulation, the transgenerational inheritance of DNA methylation is not well understood. The genetic heritability of DNA methylation has been estimated using twin pairs, although concern has been expressed whether the underlying assumption of equal common environmental effects are applicable due to intrauterine differences between monozygotic and dizygotic twins. We estimate the heritability of DNA methylation on peripheral blood leukocytes using Illumina HumanMethylation450 array using a family based sample of 614 people from 117 families, allowing comparison both within and across generations.
Results: The correlations from the various available relative pairs indicate that on average the similarity in DNA methylation between relatives is predominantly due to genetic effects with any common environmental or zygotic effects being limited. The average heritability of DNA methylation measured at probes with no known SNPs is estimated as 0.187. The ten most heritable methylation probes were investigated with a genome-wide association study, all showing highly statistically significant cis mQTLs. Further investigation of one of these cis mQTL, found in the MHC region of chromosome 6, showed the most significantly associated SNP was also associated with over 200 other DNA methylation probes in this region and the gene expression level of 9 genes.
Conclusions: The majority of transgenerational similarity in DNA methylation is attributable to genetic effects, and approximately 20% of individual differences in DNA methylation in the population are caused by DNA sequence variation that is not located within CpG sites.
Keyword Epigenetic inheritance
Genotype imputation
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2015 Collection
UQ Diamantina Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 60 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 63 times in Scopus Article | Citations
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