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New Study Finds Anorexia Has A Genetic Link, At Least Partially

September 11, 2013
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Brett Smith for redOrbit.com – Your Universe Online

According to the National Institutes of Health, almost 3.8 million Americans will suffer from anorexia at some point in their life. Thought to be primarily psychological in nature, anorexia nervosa may have a partial genetic cause – according to a new report in Molecular Psychiatry.

“These findings point in a direction that probably no one would have considered taking before,” said study author Nicholas J. Schork, a professor at The Scripps Research Institute (TSRI).

A condition that predominantly affects women and young girls, anorexia is marked by a severe eating restriction and emaciation. Individuals with anorexia may also see themselves as fat, express perfectionism, exhibit signs of anxiety or depression, and have obsessive tendencies, said Walter Kaye, a co-author on the study and professor at the University of California, San Diego School of Medicine.

Scientists aren’t entirely sure how anorexia develops in a person, but many suspect cultural, stress, hormonal and social factors.

To explore a potential genetic factor for the condition, TSRI researchers, along with a team of international colleagues, embarked on the largest-ever genetic sequencing study of anorexia. The project was based on genetic data from over 1,200 individuals diagnosed with anorexia and almost 2,000 non-anorexic participants.

In an initial “discovery” phase of the study that included over 330 subjects, the researchers recorded the genetic variants that had already been associated to feeding behaviors or had been cited in previous anorexia studies. Out of the more than 150 genetic candidates, only a small group demonstrated a significant statistical linkage with anorexia in the study cohort.

One of the strongest initial candidates was the gene EPHX2, which is involved in the production of epoxide hydrolase 2 – an enzyme recognized for regulating cholesterol metabolism.

“When we saw that, we thought that we might be onto something, because nobody else had reported this gene as having a pronounced role in anorexia,” said Schork.

After a series of replication studies – each one involving a different group of anorexia patients and control participants, as well as different genetic analysis methods – the scientists continued to see evidence that certain variants of the EPHX2 gene occur more often in people with anorexia.

To cross-reference their findings, the study researchers used existing data from a large-scale, long-term heart disease study. They found that a subset of the implicated genetic variants can alter the normal association between weight gain and cholesterol levels.

“We thought that with further studies this EPHX2 finding might go away, or appear less compelling, but we just kept finding evidence to suggest that it plays a role in anorexia,” said Schork.

The scientists said they weren’t sure what might cause the unusual metabolism of cholesterol that would help trigger or sustain anorexia. Schork suggested that the connection makes sense as individuals with anorexia often have unusually high cholesterol levels, despite being harshly malnourished. Some weight loss studies have shown that people who develop symptoms of depression can also show an increase in cholesterol levels. Other studies have shown that cholesterol has a positive association with mood.

“The hypothesis would be that in some anorexics the normal metabolism of cholesterol is disrupted, which could influence their mood as well as their ability to survive despite severe caloric restriction,” Schork said.

He added that future studies should look into biological effects of EPHX2 and other genetic variants.


Source: Brett Smith for redOrbit.com - Your Universe Online



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