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Researchers ID Epigenetic Patterns Associated with Obesity

By a GenomeWeb staff reporter

NEW YORK (GenomeWeb News) – In a study appearing online in Science Translational Medicine today, researchers from the US and Iceland reported that they have identified parts of the genome in which methylation patterns varies — including a handful of these so-called variably methylated regions that correspond to body mass index.

By comparing DNA methylation patterns across the genomes of dozens of Icelandic individuals using blood samples collected in 1991 and 2002, the team detected hundreds of regions in the genome showing variable methylation patterns from one individual to the next. Even so, they explained, many of these epigenetic marks are stable within the same individual over time.

And because more than a dozen of the variably methylated regions, or VMRs, showed some association with BMI, the researchers speculated that such epigenetic patterns could offer insights into genes and parts of the genome contributing to BMI and other conditions.

"Epigenetics has given us 13 exciting new leads to variability in body mass and obesity," co-corresponding author Daniele Fallin, an epidemiology researcher with the Johns Hopkins Bloomberg School of Public Health, said in a statement. "The team's success suggests a new epigenetic strategy for identifying those at risk for many common diseases, and for possible new prevention methods and therapies."

Fallin and her co-workers relied on a method called comprehensive array-based relative methylation using custom NimbleGen HD2 arrays to assess CpG methylation status at roughly 4.5 million sites across the genomes of 74 Icelandic individuals.

DNA for the study was isolated from the white blood cells of a subset of individuals participating in the Reykjavik study and a related project known as the Age, Gene/Environment Susceptibility, or AGES, study. In particular, the researchers focused on Reykjavik study samples collected in 1991 and AGES study samples collected from the same individuals in 2002.

In the process, they identified 227 regions of the genome in which DNA methylation varied widely from one individual to the next.

When they compared samples from 1991 with those taken in 2002, the team found that about half of VMRs for each individual showed the same patterns as they had 11 years earlier.

Meanwhile, roughly a third of the VMRs varied within the same individual over time, the researchers explained, while information for the remaining VMRs was ambiguous.

By bringing together VMR and BMI data, the researchers were also able to pin down 13 VMRs that are apparently associated with BMI.

Of these, four were consistently associated with BMI in the individuals tested, showing methylation levels that coincided with BMI. Among them: VMRs in and around PM20D1, MMP9, PRKG1, RFC5 — genes suspected of contributing to obesity, energy balance, or diabetes-related processes.

Although they noted that the findings are preliminary and based on a modest sample size, those involved in the study say it raises the possibility that some methylation marks in the genome are stable over time, while others shift — perhaps coinciding with an individual's environmental exposures.

"[T]hose regions that do not change over time can be used as an epigenetic signature for an individual, similar to genotype," they argued. "These regions can then be considered as candidates for assessment of methylation associations with disease or health-related phenotypes under specific risk models."

In the future, the team reportedly plans to do additional research investigating the potential role of VMRs in other traits or conditions such as aging and bipolar disorder.

"What we accomplished is a small proof-of-principle study that we think is just the tip of the iceberg in using epigenetics to expand our knowledge of new markers for many common diseases and opening the door for personalized epigenetic medicine," co-lead author Andrew Feinberg, director of the Johns Hopkins' Institute for Basic Biomedical Sciences' Center for Epigenetics, said in a statement.

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