Anorexia nervosa originates from a combination of psychiatric and metabolic factors, suggests a new genome-wide association study. Succeeding and reinforcing earlier, smaller studies, the new study identifies eight genetic variants that are significantly associated with the eating disorder, a life-impairing illness characterized by dangerously low body weight, an intense fear of gaining weight, and a lack of recognition of the seriousness of the low body weight.

“Until now, our focus has been on the psychological aspects of anorexia nervosa such as the patients’ drive for thinness,” said the study’s principal investigator, Cynthia M. Bulik, PhD, FAED, founding director of the University of North Carolina Center of Excellence for Eating Disorders. “Our findings strongly encourage us to also shine the torch on the role of metabolism to help understand why individuals with anorexia frequently drop back to dangerously low weights, even after therapeutic renourishment.”

Bulik, who is also a distinguished professor in the department of psychiatry in the UNC School of Medicine, added, “A failure to consider the role of metabolism may have contributed to the poor track record among health professionals in treating this illness.” According to the National Center of Excellence for Eating Disorders, anorexia nervosa has the highest mortality rate of any psychiatric illness.

Detailed findings appeared June 15 in the journal Nature Genetics, in an article titled, “Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa.” The article describes how Bulik and a multinational group of more than 100 researchers combined data collected by the Anorexia Nervosa Genetics Initiative (ANGI) and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED). The resulting data set included 16,992 anorexia nervosa cases and 55,525 controls of European ancestry from 17 countries across North America, Europe, and Australasia.

“The genetic architecture of anorexia nervosa mirrors its clinical presentation,” the article’s authors wrote. “[It shows] significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index.”

In other words, the genetic factors associated with anorexia nervosa overlap with those implicated in other psychiatric disorders such as obsessive-compulsive disorder, depression, anxiety, and schizophrenia. Genetic factors associated with anorexia nervosa also influence physical activity, which could help explain the tendency for people with anorexia nervosa to be highly active.

Intriguingly, the genetic basis of anorexia nervosa overlaps with metabolic (including glycemic), lipid (fats), and anthropometric (body measurement) traits, and the study shows that this is not due to genetic effects that influence body-mass index.

“Elucidating the metabolic component is a critical direction for future research,” the article’s authors declared. “Paying attention to both psychiatric and metabolic components may be key to improving outcomes.”

“Metabolic abnormalities seen in patients with anorexia nervosa are most often attributed to starvation,” noted Gerome Breen, PhD, a professor of psychiatric genetics at King’s College London and a co-leader of the current study. “But [these abnormalities] may also contribute to the development of the disorder. These results suggest that genetic studies of eating disorders may yield powerful new clues about their causes and may change how we approach and treat anorexia.”

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