More Epigenomic Differences Found in Twins?

Twins may look alike, and even share identical genomes, but according to new studies, their epigenomes can be surprisingly different. Examination of the DNA methylation patterns in sets of twins revealed that early environmental conditions can alter epigenomes, and have a big impact on individual variability.

A research effort headed up by Jeff Craig and Richard Saffery at Australia’s Murdoch Childrens Research Institute compared the contributions of genetic and environmental factors to phenotypic variability. The scientists profiled DNA methylation status at about 20,000 CpG sites, from three separate tissues; in groups of monozygotic (MZ) and dizygotic (DZ) twins just after birth, and were able to determine which variation was the result of environmental differences.

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“We wanted to start to answer the questions of what makes identical (monozygotic) twins different and when does this occur? Measuring DNA methylation in twins at birth is a great start because it focuses on the period spent in the womb and allows us use the classic twins model to tease apart genetics, shared and non-shared environment.” Explained Craig.

Craig, Saffery and company dusted off the old classical genetics favorite; the twin study design, to tackle the project, and got really interesting results from their analyses of 22 MZ and 12 DZ twin pairs:

  • MZ twins generally had less DNA methylation discordance than DZ pairs, but still showed a wide range of within-pair differences at birth.
  • Within-pair methylation differences were lowest in CpG islands and increased with distance from the islands.
  • Heritability of DNA methylation across all tissues was low, but a wide variety of heritability was detected for specific genomic CpG sites.
  • The largest contribution to this variation was linked to non-shared intrauterine environments and stochastic factors.
  • A general association between birth weight and the DNA methylation of metabolism and biosynthesis genes was seen through regression analysis, strengthening the link between low birth weight and an increased risk for cardiovascular, metabolic, and other diseases.
  • Data comparisons with several older twins showed little evidence for genome-wide epigenetic drift as the twins get older.

“What surprised us was that some monozygotic twins can be more epigenetically different than some unrelated individuals and that non-shared environment was by far the largest component of neonatal epigenetic variance.” Commented Craig.

This is the first study to analyze genome-scale DNA methylation in twins at birth, and it demonstrates the importance of the intrauterine environment on the neonatal epigenome, but there is still much work left to be done. As Craig puts it “Future studies can try to pick apart which non-shared environments are the most important. More studies are also needed to link early epigenetic biomarkers to disease risk.”

Jeff Craig presented some of his team’s work at the recent Australian EpiAlliance Epigenetics Meeting.

You can also find the full report at Genome Research, July 2012.