“These findings point in a direction that probably no one would have considered taking before,” said lead researcher Nicholas J. Schork, Ph.D., a professor at The Scripps Research Institute (TSRI).
Individuals with anorexia nervosa tend to be perfectionistic, anxious or depressed, and obsessive, said co-author Walter Kaye, M.D., professor at the University of California (UC), San Diego School of Medicine and principal investigator of the Price Foundation Genetic Studies of Anorexia Nervosa.
How the disorder develops is still not fully understood, but studies suggest that genetic factors have the greatest influence. Researchers believe that many genes can contribute to anorexia, and therefore only large studies will have the statistical power to detect those individual genetic influences.
For the study — the largest-ever sequencing study of anorexia — researchers analyzed genetic information from more than 1,200 anorexia patients and nearly 2,000 non-anorexic control participants.
One of the strongest signs came from the gene EPHX2, which codes for epoxide hydrolase 2 — an enzyme known to regulate 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.
The team followed up with several more studies and continued to find evidence that certain variants of EPHX2 occur more frequently in people with anorexia.
“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.
It’s still unclear how EPHX2 variants-that cause an abnormal metabolism of cholesterol-would help trigger or maintain anorexia. But Schork said that people with anorexia often have remarkably high cholesterol levels in their blood, even when they are severely malnourished.
Furthermore, other studies have suggested that weight loss, such as occurs in people with depression, can lead to higher cholesterol levels. At the same time, there is evidence that cholesterol has a positive effect on mood. This helps explain why some anorexics say they feel an improved mood, via higher cholesterol, when they don’t eat.
“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,” said Schork.