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Epigenome Varies With Body Mass Index

In a genome-wide scan, researchers found over 200 DNA regions with epigenetic modifications that vary between people. About half appear stable over time and form a personalized epigenetic “signature.” Four regions varied with body mass index, a finding that may pave the way toward new insights into how extra pounds affect your health.

Epigenetics is the study of factors that change the way genes are read, or expressed, without changing the DNA sequence itself. Epigenetic changes have been linked to several diseases over the past few years, raising the possibility that researchers might learn how to manipulate epigenomic factors to prevent or treat disease.

Methylation is a common epigenetic modification that affects gene expression. A research team led by Drs. Daniele Fallin and Andrew Feinberg at Johns Hopkins University previously found that methylation patterns can change as people age. For the new study, they wanted to further explore methylation patterns over time and between people. They also wanted to see whether any specific regions could be linked to disease risk. The study was supported by NIH’s National Institute of Environmental Health Sciences (NIEHS), National Institute on Aging (NIA), National Human Genome Research Institute (NHGRI) and others. The team also included scientists at NIA.

The researchers analyzed DNA from 74 people who gave samples 11 years apart in a study in Reykjavik, Iceland. Using an approach called comprehensive high-throughput array-based relative methylation (CHARM) that Feinberg helped to develop, the scientists searched for patterns of change over time among over 4 million methylation sites.

As reported in the September 15, 2010, issue of Science Translational Medicine, the scientists identified 227 regions that varied significantly between people. About half appeared to be stable over time within individuals, defining a personalized epigenomic signature.

To explore whether DNA methylation might play a role in disease risk, the researchers compared methylation patterns with body mass index, which has been linked to many health problems, including diabetes, heart disease and stroke. They found 13 regions that varied with body mass index. Of these, 4 had methylation patterns that consistently correlated with body mass index across the 11 years. These were all located in or near genes previously implicated in regulating body weight or diabetes.

“Some of the genes we found are in regions of the genome previously suspected but not confirmed for a link to body mass index and obesity,” Feinberg says. “Meanwhile, others were a surprise, such as one known to be associated with foraging behavior in hungry worms.”

Researchers have been debating the significance of DNA methylation and other epigenomic modifications. These results suggest that some DNA regions vary between people but remain essentially stable over time, while others can be altered by environmental factors and may contribute to diseases and disorders.

“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,” Feinberg says.

—by Harrison Wein, Ph.D.