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| Status |
Public on Jul 18, 2012 |
| Title |
Neonatal DNA methylation profile in humans is specified by a complex interplay between intrauterine environmental/ genetic factors subject to tissue-specific influence |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by array
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| Summary |
Comparison between groups of monozygotic (MZ) and dizygotic (DZ) twins enables an estimation of the relative contribution of genetic, shared and non-shared environmental factors to phenotypic variability. Using DNA methylation profiling of ~20,000 CpG sites as a phenotype, we have examined discordance levels in multiple tissues in neonatal twins. MZ twins exhibit a wide range of within-pair differences at birth, but show discordance levels generally lower than DZ pairs. Within-pair methylation discordance was lowest in CpG islands in all twins and increased as a function of distance from islands. This was largely independent of distance from transcriptional start site in promoters without CpG islands. Variance component decomposition analysis of DNA methylation in MZ and DZ pairs revealed a low mean heritability across all tissues, although a wide range of heritabilities was detected for specific genomic CpG sites. The largest component of variation was attributed to the combined effects of non-shared intrauterine environment and stochastic factors. Regression analysis of methylation on birth weight revealed a general association between methylation of genes involved in metabolism and biosynthesis, providing further support for epigenetic change in the previously described link between low birth weight and increasing risk for cardiovascular, metabolic and other complex diseases. Finally, comparison of our data with that of several older twins, revealed little evidence for genome-wide epigenetic drift with increasing age. This is the first study to analyse DNA methylation on a genome scale in twins at birth, further highlighting the importance of the intrauterine environment on shaping the neonatal epigenome.
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| Overall design |
Data from cord blood mononuclear cells (CBMCs), human umbilical vascular endothelial cells (HUVECs) and placenta from 22 MZ and 11 DZ pairs with one replicate sample
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| Contributor(s) |
Gordon L, Joo EJ, Powell JE, Ollikainen M, Novakovic B, Li X, Andronikos R, Cruickshank MN, Conneely KN, Smith AK, Alisch RS, Morley R, Carlin J, Visscher PM, Craig JM, Saffery R |
| Citation(s) |
22800725 |
| Submission date |
Mar 20, 2012 |
| Last update date |
Jan 02, 2015 |
| Contact name |
Richard Saffery |
| E-mail(s) |
richard.saffery@mcri.edu.au
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| Organization name |
Murdoch Children's Research Institute
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| Department |
Cancer, Disease and Developmental Epigenetics
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| Lab |
Cancer, Disease and Developmental Epigenetics
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| Street address |
Flemington Rd
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| City |
Parkville |
| State/province |
Victoria |
| ZIP/Postal code |
3052 |
| Country |
Australia |
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| Platforms (1) |
| GPL8490 |
Illumina HumanMethylation27 BeadChip (HumanMethylation27_270596_v.1.2) |
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| Samples (123)
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| Relations |
| BioProject |
PRJNA153645 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE36642_RAW.tar |
5.8 Mb |
(http)(custom) |
TAR |
| GSE36642_intensities_CBMCs.txt.gz |
19.2 Mb |
(ftp)(http) |
TXT |
| GSE36642_intensities_HUVECs.txt.gz |
15.1 Mb |
(ftp)(http) |
TXT |
| GSE36642_intensities_placenta.txt.gz |
6.4 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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