First Genetic Variant Identified For Anorexia Nervosa
A genomewide analysis of thousands of samples also identifies several links between anorexia and metabolic traits such as obesity, cholesterol levels, and insulin resistance.
An international research consortium has uncovered the first genetic variant associated with anorexia nervosa, a serious and potentially lethal eating disorder that affects around 1 percent of the population. The identified variant, known as rs4622308, is found on chromosome 12 and has been previously linked with both type 1 diabetes and rheumatoid arthritis.
This groundbreaking study was published May 12 in AJP in Advance.
Study co-author Cynthia Bulik, Ph.D., Distinguished Professor of Eating Disorders at the University of North Carolina School of Medicine, told Psychiatric News that the findings of this genomewide analysis go beyond one single variant.
“Our foot is on the accelerator now,” she said. “Once we find one genetic locus, it puts us on a trajectory to find many more.”
Bulik explained that methodologically, the researchers have a handle on how big a sample size they need to uncover similar variants. This study analyzed genomes of 3,495 anorexia nervosa cases and 10,982 controls, and 13,000 additional anorexia samples are queued up for the next round.
In addition, with some potential genes identified, the researchers can also do more targeted studies. This rs4622308 variant overlapped six genes, and six other genes were close enough to potentially be affected by the variant.
What really intrigued the team, however, was the genetic correlations they uncovered between anorexia and other medical and psychosocial traits. They found a strong association among anorexia, neuroticism, and schizophrenia, which reinforces many clinical and epidemiological observations showing these traits co-occurring.
Also, there were several genetic correlations with metabolic parameters; people with anorexia tended to have more favorable variants associated with cholesterol levels, while far fewer variants associated with obesity or insulin resistance.
“For the longest time, anorexia has been seen as a purely psychiatric illness,” Bulik said. “These findings should make us reconsider.”
Bulik noted that she has frequently been asked whether anorexia is the opposite of obesity, and her answer until now had been no. “I had always believed constitutional fitness, the ability to eat and not gain weight, was the comparable bookend to obesity. But I think I might be wrong, especially given the strong genetic correlation between anorexia and BMI.”
As highlighted in the article, Bulik thinks that these correlations might explain the similarities seen in people with morbid obesity or anorexia undergoing treatment. While controlled dietary interventions can bring people back to normal weights, patients quickly revert to their high or low weights once the programs end.
More research is needed to make the connections between these disorders stronger, but Bulik thinks it might be time to change how disorders of appetite dysregulation are conceptualized and instead think of both anorexia and obesity as having psychiatric and metabolic components (currently obesity or food addiction are not classified as mental disorders).
In addition to the next batch of anorexia samples, Bulik and her colleagues are launching another genomewide study to identify variants associated with bulimia, and in the future, they hope to test how the microbiome may work along with genetic profiles to influence eating disorders.
This international study was supported by multiple sources, including grants from the National Institutes of Health, Australia’s National Health and Medical Research Council, German Research Foundation, and more. A complete list can be accessed at the link below. ■
“Significant Locus and Metabolic Genetic Correlations Revealed in Genome-Wide Association Study of Anorexia Nervosa” can be accessed here.
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Published online: 15 June 2017
Published in print: June 3, 2017 – June 16, 2017
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