Rethinking eating disorders as both psychiatric and metabolic 

10 March 2020

Kindly provided by the Eating Disorders Genetics Initiative

New Zealand researchers are transforming our understanding of genetic factors that influence the primary eating disorders—anorexia nervosa, bulimia nervosa, and binge-eating disorder (BED). Historically, eating disorders were thought to be caused primarily by societal (preoccupation with thinness) and personality (perfectionism) factors. However, recent work, the Anorexia Nervosa Genetics Initiative (ANGI), that included New Zealand scientists and participants, and appeared in Nature Genetics, has shown that on a genetic level, anorexia nervosa has not only psychiatric, but also metabolic origins. An extension of ANGI, the Eating Disorders Genetics Initiative (EDGI), also being conducted in New Zealand and other sites around the world, will expand the science to explore similar questions about the genetic underpinnings of all three eating disorders.

Anorexia nervosa is characterized by dangerously low body weight and indifference to the seriousness of the illness; has poor outcomes, particularly in adults; and high mortality. To date no medications exist that target its core features. Bulimia is characterized by binge eating and compensatory behaviours (e.g., self-induced vomiting, misuse of laxatives). Recovery rates are around 50% at 5-10 years follow-up. BED is the most common eating disorder and is characterized by recurrent binge eating (without regular compensatory behaviours) and is often accompanied by obesity and metabolic syndrome.  

Eating disorders affect a diverse range of people including males, gender diverse people, and ethnic minorities, although these diverse groups are less likely to be seen in treating services, in part due to underdetection. Onset can occur at any age, most commonly adolescence or early adulthood, and outcome is better when detected and treated early.

Genetic studies of anorexia nervosa

We knew from twin studies that eating disorders run in families and that genes play a role. A contemporary approach called a genome-wide association studies (GWAS) places markers across complete sets of DNA (genomes) of many people with the condition compared to unaffected controls to identify specific differences in the genome. Extremely large samples (tens of thousands of cases) are required for GWAS.

The ANGI study

ANGI recruited the largest sample of anorexia nervosa ever amassed. New Zealand contributed 555 of almost 17,000 participants which were compared to over 55,000 controls from 17 countries across North America, Europe, and Australasia.

We found eight genetic variants to be significantly associated with anorexia nervosa. But, the most interesting finding was that many genetic factors associated with anorexia nervosa overlapped with genetic factors that influence:

  1. other psychiatric disorders such as obsessive-compulsive disorder, depression, anxiety, and schizophrenia
  2. physical activity levels
  3. metabolic traits (such as insulin and lipid levels)
  4. anthropometric (body measurement) traits, such as BMI and fat mass 

These findings confirm clinical observations, namely that anorexia nervosa often co-occurs with other psychiatric illnesses. Now we know that the co-occurrence is likely due to shared genetic factors. 

Second, on a genetic level, anorexia nervosa appears to be both a psychiatric and a metabolic illness—explaining some of the most perplexing facets of the illness. The results clarify why people with anorexia nervosa struggle to gain weight despite their best efforts. Metabolic factors may play a central role. 

ANGI has immediate clinical implications. First, they underscore the importance of full weight restoration rather than a low target weight. Metabolic factors may explain why the risk of “weight relapse” is so high and highlight the importance of allowing the body to adjust metabolically after weight restoration.

Where to from here?

This week the New Zealand arm of the Eating Disorders Genetics Initiative (EDGI) will be launched, with the aim of recruiting 3,500 New Zealand participants with a lifetime history of anorexia nervosa, bulimia nervosa, or BED. Participants will complete online surveys and provide a saliva sample for genetic analysis. 

EDGI will further enhance our understanding of the biological underpinnings of all eating disorders and clarify why some individuals are more vulnerable to developing these pernicious illnesses than others. Ultimately, our goal is to use the newfound genetic knowledge to develop novel and more effective treatment approaches informed by biology that will reduce medical and psychiatric morbidity and eliminate mortality from eating disorders. We hope that practitioners across New Zealand will encourage individuals with eating disorders to visit our website and participate in EDGI.

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