Epigenetics: A Fascinating Problem

In the beginning, scientists had a simple hope: one gene, one disease.

Then they discovered that dozens, even hundreds of genes, might play roles in causing disease.

Then they found that epigenes—the chemical modifications to genes that control whether or not genes are expressed—have a part as well.

Then they learned that whether a genetic mutation is inherited from the mother or father may be important in disease causation.

Then they learned that toxins or other environmental agents—perhaps even stress—can alter epigenes, which can then lead to disease.

Now, they think the timing of an environmental exposure may determine whether or not the disease cascade begins.

Wildly complex?  Genetic epidemiologist M. Daniele Fallin agrees: “It’s horrible but fascinating at the same time. It really is a challenge of, ‘How are we ever going to solve this?’ The best advice I have is to tackle one thing at a time while realizing there is a broader context.”

So Fallin is starting at the beginning. Actually, before the beginning. Her EARLI study will follow children at risk of autism from before they are even born through their third birthday (by which time autism symptoms usually are manifest). By following a group of 1,000 pregnant women who already have given birth to an autistic child, Fallin and colleagues from three sites across the nation hope to elicit patterns in the intricate interplay of genes, epigenes, environment and time that can result in autism.

Fallin’s team is collecting blood samples from women in their second and third trimester of pregnancy, cord blood, and then blood from the babies at three or six months and two or three years. They also will take dust samples from the women’s homes, ask them to keep a weekly diet and behavior diary, as well as noting exposures to tobacco smoke and alcohol among other factors. For help with the burgeoning complexity of the study, as well as the mountain of samples and data she’s collecting, Fallin is partnering with epigeneticist Andy Feinberg and biostatistician Rafael Irizarry.

The autism-specific EARLI study complements the much larger, broader National Children’s Study (NCS), whose ambitious goal is to follow 100,000 children from before birth to age 21. NCS’s goal is to elucidate the genetic, epigenetic and environmental links to autism as well as asthma, diabetes, birth defects and other conditions. Despite their expense and difficulty, such longitudinal studies are the best way right now to break the mystery of disease causation, according to Lynn Goldman, principal investigator for the NCS Center at the School and a professor of Environmental Health Sciences. “When we look at something like autism or asthma, we are looking a complex condition that has multiple factors that  are going to require not only longitudinal approaches and epidemiological approaches, but also laboratory-based approaches and thinking,” says Goldman.

Fallin agrees that the only way to make future breakthroughs in the thicket of disease causation is to involve experts from biostatistics, environmental epidemiology, genetic epidemiology and other fields. Previously in autism and other research, proponents of genetic causes and those who suspected environmental links didn’t mix much, she says.

“The real take-home of interest is that this is a real, true partnership of environmental epidemiologists and genetic epidemiologists. It takes all those different players to see how this is going to play out,” Fallin says.