Since the founding of Kartini Clinic in 1998 we have operated under the assumption (then almost unheard-of) that anorexia nervosa is a biologically based, heritable human illness of the brain. For that reason we have always taken detailed family histories, and later in the early 2000’s began contributing towards what became a giant genetic study, and now at last reported on by lead author Cindy Bulik. On July 15th the results of the study were published in Nature Genetics: Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa (behind a paywall, unfortunately).

This is a major milestone in understanding the biology and heritability of this devastating illness. Kartini providers Dr. Julie O’Toole and Dr. Janiece Desocio are proud to have their names among the many on this paper. 

Dr. Bulik et al. have put together some summary talking points of the study. Please note some of the paradigm-busting comments:

  • “occurs in all racial and economic backgrounds and socioeconomic classes” and is “stable across time”, i.e. not a modern disease

  • “there is more to anorexia nervosa than just the psychological components...it is a metabo-psychiatric disorder” 

  • No longer is there any reason to view anorexia nervosa as a “choice”, a “result of flawed parenting” “a result of the oppression of women” or “caused by the media or bullying”

What is anorexia nervosa?

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 low body weight.

How common is anorexia nervosa?

The prevalence of anorexia nervosa is between ~1-4% in women and 0.3% in men and appears to be stable across time.

Who gets anorexia nervosa?

Anorexia nervosa does not discriminate. Although the most common age of onset is adolescence, anorexia nervosa can occur at any time of life, all sexes, genders, racial and ethnic backgrounds and socioeconomic classes.

What is a genome-wide association study (GWAS)?

A genome-wide association study involves scanning markers across complete sets of DNA, or genomes, of many people with a particular illness (such as anorexia nervosa) compared to controls. By identifying where differences in the genome lie, researchers can identify genetic variations associated with the illness. Once new genetic associations are identified, researchers can use the information to develop better strategies to detect, treat, and prevent the disease. Such studies are particularly useful in finding genetic variations that contribute to common, complex diseases, such as asthma, cancer, diabetes, heart disease and mental (brain) illnesses.

What is the Anorexia Nervosa Genetics Initiative (ANGI)?

Is an initiative of the Klarman Family Foundation who supported the largest single collection of samples from individuals with anorexia nervosa and controls ever performed. The study was based at the University of North Carolina at Chapel Hill and included researchers from Karolinska Institutet in Stockholm Sweden, Aarhus University, in Aarhus Denmark, Berghofer Queensland Institute for Medical Research, Brisbane Australia with assistance from the University of Otago in New Zealand. ANGI contributed 13,363 cases to the GWAS.

What are the details of the study? How many people participated?

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.

What were the main findings and results?

  • The GWAS identified eight genetic variants significantly associated with anorexia nervosa.

  • 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 even when acutely ill.

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

What does this mean for patients and families now?

It is helpful for patients and families to understand that there is a biological basis for anorexia nervosa. It is a perplexing and potentially fatal illness that is challenging to recover from and takes an enormous toll on individuals with the illness and their loved ones. These results offer hope that we may be on the right path to understanding the biology of the illness that may eventually allow us to develop novel therapeutics to treat this often intractable disorder.

Why call it a metabo-psychiatric disorder?

The panel of genetic correlations that we reported strongly suggest that there is more to anorexia nervosa than just the psychological component. The fact that we observed genetic correlations with a whole host of metabolic and anthropometric traits may explain some of the most perplexing aspects of anorexia nervosa such as: how can they reach such low body mass indices in the first place, how can they remain at such low body weights, why is it so hard for them to maintain a healthy body weight even after treatment, and why are our treatments inadequate to help them achieve full recovery? 

This could explain why adequate renourishment is so critical to long term recovery. Stopping treatment before reaching and maintaining a healthy BMI may destine someone with anorexia nervosa to relapse. 

Will there be gene-therapy for anorexia nervosa in the future? What’s next?

No and this is not the long term goal of this type of science. The goal of GWAS is to elucidate biology. Part of the reason that we have no medications that are effective in the treatment of anorexia nervosa is because the biology of the illness remains a mystery. We expect that hundreds and even thousands of genes will be implicated in risk for anorexia nervosa combined with environmental factors, meaning that anorexia nervosa is a classic “complex disease.” We hope that with increasing sample size, we will be able to identify underlying biological pathways that can give us insight into how these genes influence anorexia nervosa—and now we know to look not only at pathways that influence psychiatric factors, but also metabolic ones.

Future studies?

Even though almost 17,000 sounds like a large study, it is still small by GWAS standards. Our goal is to reach 100,000 anorexia nervosa cases with appropriate controls. Other psychiatric disorders have reached this milestone with intriguing results. We then need to do the same for the other eating disorders (bulimia nervosa, binge-eating disorder, and avoidant/restrictive food intake disorder-ARFID). We have a lot of work ahead and it will take a global effort to reach our goals.