New tool could help researchers pinpoint the genetic sources of disease

Many diseases have their origins either in the genome or in reversible chemical changes to DNA known as the epigenome. Now, results of a new study from Johns Hopkins scientists show a connection between these two maps.

The findings, reported last week on the website of the American Journal of Human Genetics, could help disease trackers find patterns in those overlays that could offer clues to the causes of—and possible treatments for—complex genetic conditions, including many cancers and metabolic disorders.

"By showing the connections between genetic variants and epigenetic information, we're providing epidemiologists with a road map," says Andrew Feinberg, professor of medicine and the director of the Center for Epigenetics at the Johns Hopkins University School of Medicine. "Epigenetic tags show how disease-causing genetic variants might affect distant genes that in turn contribute to the disease."

It has long been known, Feinberg says, that individual genetic variants in sections of DNA that don't contain blueprints for proteins—once thought of as "junk DNA"—seem to alter the quantity of proteins produced far afield. That phenomenon has made it very hard for researchers to pinpoint the source of some genetic diseases or to identify targets for their treatment. This study, Feinberg says, shows that these genetic variants may be acting on distant protein-forming genes by influencing epigenetic tags, or chemical add-ons, atop the DNA.

Feinberg says he hopes that researchers will see these findings as a reason to add epigenetic analyses to ongoing genetic analyses of disease. His group's next step, he says, will be to look for signatures associated with specific diseases, such as Crohn's and cirrhosis, in which researchers have struggled to isolate the problematic part of the genetic code. "Researchers—ourselves included—can use this information," says Feinberg, "to see if the implicated gene is turned on or off in patients compared to healthy people."