Anorexia nervosa is difficult to predict and, if left untreated, potentially life-threatening. How the eating disorder develops is poorly understood, though genetics has long been thought to be a factor. A novel new study has narrowed down a gene connected to cholesterol metabolism as possibly playing a large part. The study, conducted by an international team of collaborators representing over 25 institutions, was the largest ever DNA-sequencing study of anorexia nervosa. Nicholas J. Schork of The Scripps Research Institute was senior investigator. Anorexics severely restrict caloric intake, viewing themselves as overweight even when painfully thin. As a result the disorder is fatal for at least 10 percent of those afflicted. Certain personality traits and problems are linked to the eating disorder, including perfectionism, obsession, depression and anxiety. Schork and his fellow investigators looked at genetic data from 1,205 cases and 1,948 control subjects without anorexia. The team found that the gene EPHX2, which informs an enzyme involved with cholesterol processing, seemed to appear more abundantly in a high number of the anorexics studied. The researchers performed several follow-up studies which confirmed the connection between anorexia and cholesterol, as well as showing increased presence of EPHX2 and its variants in persons with anorexia compared to the control subjects. The researchers are unable to explain how the inefficient metabolizing of cholesterol affects anorexia. Further study has shown that those with anorexia do have abnormally high levels of cholesterol regardless of how poorly they’ve been eating. Separate studies show that depression-related weight loss sometimes elevates cholesterol. This would be consistent with the cholesterol-anorexia link. Yet people with anorexia have been known to say that restricting food intake makes them feel happier, not depressed. And cholesterol has been connected to positive mood. Why a depressed person would have high cholesterol with none of the positive mood benefits is confounding. On the other hand, since higher levels of cholesterol have been connected to positive mood, having more cholesterol in their blood might explain how starving themselves could actually make the anorexic person feel better. Furthermore, the increased cholesterol could also be a protection against the ravages of severely restricted food intake.