Genetic Markers for Anorexia Nervosa
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Researchers identify anorexia nervosa genetic variants, redefine disorder as metabolic and psychiatric.
The large-scale genome-wide association study, led by UNC’s Cynthia M. Bulik, PhD, FAED, founding director of the UNC Center of Excellence for Eating Disorders, and Gerome Breen, PhD, of King’s College London suggests that the origins of the eating disorder include a combination of metabolic and psychiatric components.
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A new large-scale genome-wide association study published in Nature Genetics, has identified eight genetic variants significantly associated with anorexia nervosa; and the research shows that the origins of this serious disorder appear to be both metabolic and psychiatric.
Anorexia nervosa is 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. Anorexia nervosa has the highest mortality rate of any psychiatric illness, according to the National Center of Excellence for Eating Disorders.
“Until now, our focus has been on the psychological aspects of anorexia nervosa such as the patients’ drive for thinness. 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. A failure to consider the role of metabolism may have contributed to the poor track record among health professionals in treating this illness,” said principal investigator Cynthia M. Bulik, PhD, FAED, founding director of the UNC Center of Excellence for Eating Disorders and Distinguished Professor in the Department of Psychiatry in the UNC School of Medicine.
For the study, 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.
Oregon Research Institute senior scientist Andrew W Bergen, Ph.D., contributed to this effort through a collaboration that has provided genome-wide genotype data on a collection of over 1,000 anorexia nervosa patients to multiple genome-wide association studies of anorexia nervosa over the past decade.
Other findings of the study include:
• The genetic basis of anorexia nervosa overlaps with 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 BMI.
Dr. Gerome Breen of King’s College London, who co-led the study said, “Metabolic abnormalities seen in patients with anorexia nervosa are most often attributed to starvation, but this study shows they 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.”
The study concludes that anorexia nervosa may be a ‘metabo-psychiatric disorder’ and that it will be important to consider both metabolic and psychological risk factors when exploring new avenues for treating this potentially lethal illness.
Researchers from over 100 institutions worldwide participated in the study.
The Anorexia Nervosa Genetics Initiative (ANGI) is an initiative of The Klarman Family Foundation. ANGI was led by Dr. Bulik at the University of North Carolina at Chapel Hill with collaborators from Karolinska Institutet, Stockholm, Sweden (Dr. Mikael Landén), Aarhus University, Aarhus, Denmark (Dr. Preben Bo Mortensen), and Berghofer Queensland Institute for Medical Research, Brisbane, Australia (Dr. Nick Martin) with assistance from the University of Otago, Christchurch New Zealand (Drs. Martin Kennedy and Jenny Jordan). ANGI contributed 13,363 cases to the GWAS. Drs. Bulik and Breen co-chair the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED), which contributed the second largest number of samples and is expanding these studies to include other eating disorders as well.
Funding was provided by The Klarman Family Foundation, the U.S. National Institute of Mental Health, the UK National Institute for Health Research, and the Foundation of Hope, Raleigh, NC.