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Researchers have discovered biological evidence of a genetic underpinning to anorexia nervosa: genetic linkage on chromosome 1 for the complex psychiatric disorder.

"This is the first genetic linkage finding we have in anorexia, so we're quite excited," notes the study's first author, Dorothy Grice, MD, of the University of Pennsylvania's department of psychiatry and Center for Neurobiology and Behavior.

Linkage refers to the greater-than-chance likelihood that two separate DNA sequences will be close to one another on the same chromosome, supplying biological evidence for a genetic trait if seen among two or more family members.

The findings, reported in this month's issue of the American Journal of Human Genetics, support data from twin and family studies suggesting that biology does indeed account, at least in part, for the disorder.

The findings add a new dimension to a field that has posited mainly psychological, family and sociocultural roots to the disorder, notes University of Pittsburgh psychiatrist Walter Kaye, MD, who heads the large international multisite project on the genetics of eating disorders, of which the study is a part.

"Anorexia and bulimia are considered disorders that are psychosocial in origin," Kaye says. "Recently, there's been accumulating evidence for contributory biological, family and genetic components. I suspect we're going down the path we did with schizophrenia and autism 20 years ago"--that is, that anorexia, like these other psychiatric disorders, appears to have genetic susceptibilities.

It's likely that several genes predispose people to the disorder, points out Cynthia Bulik, PhD, a Virginia Commonwealth University psychologist who is a leading investigator of eating disorders. She and other researchers hope the finding will lead to new treatments for the condition, which although it has a low incidence in the general population, has the highest mortality rate of any mental health disorder.

A GENETIC PREDISPOSITION

Using genetic linkage analysis, the study compared DNA samples of people suffering from anorexia nervosa with those of family members who also have an eating disorder, noting where on a person's "genetic map" certain genetic markers aggregated.

In a first round of the study, the team analyzed DNA of individuals from 192 family groupings. At least one of the family members had to have a diagnosis of anorexia nervosa, while one or more other family members had to display some kind of disordered eating, though not necessarily anorexia nervosa.

The analysis of the entire sample did not reveal strong potential genetic similarities among the tested relatives. However, when researchers pared the sample down to 37 families in which two or more relatives had restricting anorexia nervosa--the "classic" form marked by severe food restriction without accompanying binge-eating and purging--they found strong evidence for the possibility of a susceptibility gene or genes on chromosome 1.

The findings do not mean that the researchers have actually located a gene for anorexia nervosa, emphasizes University of Pittsburgh's Kaye.

"When you have markers in common, as some members of these 37 families do, that means a particular chromosome is more likely to contain areas of interest," Kaye notes. "If trying to identify the responsible gene is like trying to find a person in the world, then we may have located the city the person lives in. It gives you some clue that you're in the right area."

Indeed, most likely there won't be a single gene that "causes" anorexia nervosa, but rather a number of genes that dispose someone to it, adds psychologist Bulik of Virginia Commonwealth University, who was part of the research team. These genes may include ones for personality variables such as anxiety, perfectionism or perseverance, for example, or for hormonal, metabolic and appetite factors.

"This is a complex disorder," says Bulik. "All kinds of different domains might play a role. A number of genes are probably involved, each with small but modest effects."

After years of studying the disorder, Bulik agrees that focusing solely on sociocultural factors provides a limited view of the disorder.

"Sociocultural factors are only important in that they might elicit an expression of someone's pre-existing genetic predisposition," she says. The next step for investigators, says Kaye, is to narrow down which genes in the localized area of chromosome 1 may play a role and to test for those genes. In addition, the team wants to replicate the finding in a larger number of families that have two or more individuals with anorexia nervosa. (Those who want to learn more about the study, or who know families who might want to participate, can visit the project's Web site at www.anbn.org.)

TREATMENT IMPLICATIONS

Although it may take years to develop a genetic profile for anorexia nervosa, Bulik believes the new development should ultimately be seen in terms of its potential for prevention and therapy.

"Right now, our blanket approaches have not been terribly effective in preventing eating disorders," Bulik says. "If we could use an individual's genetic profile to indicate level of risk, we could develop focused and tailored prevention packages for those most susceptible to developing an eating disorder."

Gene-replacement therapy itself may also be a possibility, she adds, though that's even further down the road.

It's important to keep at such investigations, Bulik adds, because the illness is so serious.

"It's still five or six years before people start getting better--and that's with treatment," says Bulik. "If a doctor told me it was going to take me five years to get better from some illness, I'd have a hard time accepting that. If we can figure out what genes contribute to this disorder, we might be more effective in alleviating the suffering of people who experience it."

Tori DeAngelis is a writer in Syracuse, N.Y.