Identification of the First Genetic Marker for Anorexia Nervosa and Associations with Metabolic Disease

BY: Melissa Munn-Chernoff, PhD

DATE: 2 June 2017: World Eating Disorder Action Day

Last month, the very first study to identify a significant genetic marker for anorexia nervosa was published in the American Journal of Psychiatry.1 The study uncovered the possibility that anorexia nervosa may be conceptualized as both a psychiatric and a metabolic disorder, a perspective that has not been previously held.

This study was part of an international effort from the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED), which consists of over 220 scientists and clinicians from various disciplines, including researchers at CEED and Karolinska Institutet in Sweden. By including nearly 3,500 individuals with anorexia nervosa and 11,000 individuals without anorexia nervosa, we found a significant genetic locus on chromosome 12 in an area previously associated with type 1 diabetes and autoimmune disorders, such as rheumatoid arthritis. The heritability of anorexia nervosa estimated from all genetic variants assessed in the study was 20%, which is similar to other psychiatric disorders, including schizophrenia and bipolar disorder. Genetic correlations—which explore the extent to which the same genes contribute to two disorders or traits—were also examined. These correlations were investigated between anorexia nervosa and schizophrenia, neuroticism, educational attainment, weight/body mass index, and metabolic parameters. Positive genetic correlations (same genes, same direction of effect) emerged with schizophrenia, neuroticism (a personality trait associated with anxiety and major depression), years of education, and attending college. Surprisingly, there were also strong positive genetic correlations with cholesterol and lipid measures that are favorable metabolic measures. On the other hand, strong negative genetic correlations (same genes but opposite direction of effect) were observed between anorexia nervosa and obesity, extreme high BMI, and other glucose and insulin-related phenotypes associated with more unfavorable metabolic traits.

The implications of this study are tremendous. First, results confirm anorexia nervosa as a serious psychiatric illness. Second, the eating disorders field has previously focused on psychiatric components of anorexia nervosa, such as drive for thinness and weight preoccupation. However, metabolic factors, such as HDL, lipid measures, insulin, and glucose levels, may also be important. UNC’s Dr. Cynthia Bulik, the senior author on the study explains, “This pattern of results opens a window into some of the fundamental puzzles about anorexia nervosa such as how individuals prone to anorexia can actually lose and maintain such low body weights and how their bodies pull them back down to low weights even after therapeutic weight restoration.” The authors conclude that we should start thinking about anorexia nervosa as having both psychiatric and metabolic components. Bulik adds, “I am happy to have been proven wrong. Throughout my career, I have contended that anorexia nervosa is not the opposite of obesity, but now I am re-thinking that answer. At least in part, we are seeing the same genes underlying both extremes of weight dysregulation, but working in opposite directions.” Next steps for the PGC-ED is to add in all of the samples collected as part of the ANGI effort (also see below) and to dig deeper to figure out what the metabolic mechanisms are that operate in anorexia nervosa. Having a deeper appreciation of both the psychiatric and metabolic factors associated with anorexia nervosa may improve our understanding of and, ultimately, treatment for the illness.

For more information about this study, please read the UNC press release here.

For more information about ANGI, see these selected blog posts:

UNC Launches Global Effort

Dr. Cynthia Bulik Delivers ICED 2015 Keynote Address

News from the PGC and ANGI

ANGI: A Look at our Final Year of Recruitment



1Duncan L, Yilmaz Z, Gaspar H, Walters R, Goldstein J, Anttila V, Bulik-Sullivan B, Ripke S, Eating Disorders Working Group of the Psychiatric Genomics Consortium, Thornton L, Hinney A, Daly M, Sullivan PF, Zeggini E, Breen G, Bulik CM. (in press). Significant locus and metabolic genetic correlations revealed in genome-wide association study of anorexia nervosa. American Journal of Psychiatry. doi: 10.1176/appi.ajp.2017.16121402.