Scientists report finding gene mutations connected to eating disorders

Anorexia nervosa and bulimia are debilitating and occur in 1% to 3% of women, less frequently among men.
(Mark Boster / Los Angeles Times)

Scientists have discovered two gene mutations that they believe are associated with an increased risk of eating disorders.

Anorexia nervosa and bulimia often run in families, but these eating disorders are complex, and it has proved difficult to identify the paths. But, using two families with very high incidences of eating disorders, scientists say they found rare mutations, one in each family, that were associated with the people who had the disorders.

The study suggests that mutations that decrease the activity of a protein that turns on the expression of other genes – called a transcription factor – increase the risk. That transcription factor is estrogen-related receptor alpha, or ESRRA.

Anorexia nervosa and bulimia are debilitating and occur in 1% to 3% of women, less frequently among men. They are among the deadliest of psychiatric diseases. They are thought to occur as a result of a combination of genetic predisposition and environmental factors.

The scientists reported their results in Tuesday’s Journal of Clinical Investigation.


“It’s basically a matter of finding out what the people with the disorder share in common that people without the disease don’t have,” Michael Lutter, the senior author of the study and an assistant professor of psychiatry at the University of Iowa, said in a statement. One challenge, he said, is finding families large enough to provide “statistical power.”

Lutter and colleagues from Iowa and the University of Texas Southwestern Medical Center studied the DNA of people from two families significantly affected by eating disorders. In one family, scientists looked at 20 people over three generations, 10 of whom had an eating disorder. In the other family, six people with an eating disorder and two without (over four generations) were studied.

Several factors in those families suggested genetic issues in the disorders: the large percentage of affected people, the young age at which the disorder began, the extended course of the illness, and the fact that several males were affected in one of the families.

In the first family, the scientists wrote, the gene discovered was the transcription factor ESRRA. The mutation associated with the eating disorders decreases the activity of ESSRA.

The second family had a mutation that turns off transcription factors. The gene is called histone deacetylase 4, or HDAC4.

Those genes are known to be involved in muscle and fat tissue and to be regulated by exercise, the scientists said. And, they said, “several lines of evidence suggest that ESRRA and HDAC4 may have a functional interaction.”

The researchers said they planned to study the genes further in mice to learn what they are doing in the brain, as well as to study other people with eating disorders.


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