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Genomics study pieces together new anorexia links

International research has shown for the first time that anorexia nervosa is genetically linked to both metabolism and serious psychiatric conditions including schizophrenia.

May 26, 2017, updated May 26, 2017
File image: Gareth Fuller/PA Wire

File image: Gareth Fuller/PA Wire

The long-term study included genome-wide analysis of DNA from 3,495 individuals with anorexia nervosa and 10,982 unaffected individuals.

More than 200 scientists around the world, led by Professor Cynthia Bulik from the University of North Carolina School of Medicine in the US and the Karolinska Institutet in Stockholm, have worked on the landmark study described as the most powerful genetic study of anorexia nervosa conducted to date.

“We identified one genome-wide significant locus for anorexia nervosa on chromosome 12, in a region previously shown to be associated with type 1 diabetes and autoimmune disorders,” said lead investigator Professor Bulik, founding director of the UNC Center of Excellence for Eating Disorders.

“We also calculated genetic correlations – the extent to which various traits and disorders are caused by the same genes.

“Anorexia nervosa was significantly genetically correlated with neuroticism and schizophrenia, supporting the idea that anorexia is indeed a psychiatric illness.”

“But, unexpectedly, we also found strong genetic correlations with various metabolic features including body composition (BMI) and insulin-glucose metabolism. This finding encourages us to look more deeply at how metabolic factors increase the risk for anorexia nervosa,” Professor Bulik said.

Anorexia nervosa is a severe psychiatric disorder with high mortality rates. While there is evidence of a significant genetic component, the ongoing international collaboration is aiming to understand the genetic basis of the disorder.

Flinders University School of Psychology Professor Tracey Wade.

Flinders University Professor of Psychology Tracey Wade, who worked extensively with Professor Nick Martin at the Queensland Institute of Medical Research as part of the Australian research site, said: “We have long known that ‘genes loads the gun and the environment pulls the trigger’ with respect to causing anorexia nervosa.

“This is the first study to identify a specific genetic locus for anorexia nervosa that implicates metabolic processes, which opens up a new pathways to explore in terms of treatment.

“The work will continue in order to detect other relevant pathways that can inform treatment, both biological and psychiatric, such as shared genetic risk with schizophrenia.”

If particular genetic variations are significantly more frequent in people with a disorder compared to unaffected people, the variations are said to be “associated” with the disorder.

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The common roots anorexia shares with psychiatric and metabolic traits will help researchers and clinicians understand where disorder-causing problems arise and how to better treat them and develop effective interventions.

The researchers are continuing to increase sample sizes and see this as the beginning of genomic discovery in anorexia nervosa. Viewing anorexia nervosa as both a psychiatric and metabolic condition could ignite interest in developing or repurposing medications for its treatment where currently none exist.

Anorexia nervosa (AN) imposes a major health burden in Australasia and worldwide, and has a higher mortality rate than any other psychiatric disorder (Deloitte Access Economics, 2012). The causes of AN are still largely unknown.

The Australasian Anorexia Nervosa Genetics Initiative has conducted the largest study of individuals with anorexia nervosa ever assembled across Australia and New Zealand, recruiting 3,414 Australians and 543 New Zealanders to contribute to the research.

Other overseas institutions involved in the Psychiatric Genetics Consortium Eating Disorders Working Group include King’s College London, Stanford University, the Broad Institute of MIT and Harvard University, Massachusetts General Hospital, Charité-Universtätsmedizin Berlin, the department of child and adolescent psychiatry at the University of Duisburg, Essen; and the Wellcome Trust Sanger Institute.

Australian groups include the QIMR Berghofer Institute of Medical Research, University of Queensland and Royal Brisbane and Women’s Hospital in Queensland; Flinders University; University of Sydney, Western Sydney University, Sydney Children’s Hospital Network and Butterfly Foundation; Royal Children’s Hospital in Melbourne; Curtin University, Princess Margaret Hospital for Children and Centre for Clinical Interventions in Perth; Royal Hobart Hospital; and University of Otago, NZ.

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