Anorexia nervosa isn’t just a psychiatric condition – it is a metabolic one, too, according to a genetic study of around 72,500 people. The findings help to explain some of the symptoms of anorexia, and could help to shape future treatments.
Anorexia affects between 0.9 and 4 per cent of women and 0.3 per cent of men, but is still poorly understood. “Anorexia has the highest mortality rate of any psychiatric disorder,” says Cynthia Bulik at the University of North Carolina at Chapel Hill. “We’re not very good at treating anorexia. There’s no medication, and that’s probably because we don’t understand the underlying causes.”
Previous research has found that genetic factors, as well as environmental ones, can increase a person’s risk of anorexia. To investigate, Bulik and her colleagues compared the genomes of just under 17,000 people with anorexia with those of 55,500 people who didn’t have the condition.
The team used a technique that applies thousands of markers to the genome, and compares these markers across all the volunteers. “It points you to where in the genome the differences lie,” says Bulik.
The search pinpointed eight locations across the genome that seem to play a role in anorexia. But this is likely to represent only a tiny fraction of all the genetic factors involved in the condition, says Bulik. “It’s a complex trait, so we expect lots of genes to each have a small to moderate effect,” she says.
The researchers compared their results with similar genetic studies of other traits, ranging from other psychiatric conditions to weight, education and personality. They found that anorexia seems to be correlated with obsessive compulsive disorder and depression, suggesting that these all share genetic factors. This makes sense, says Bulik – people with these conditions often show similar symptoms.
The team also found a genetic correlation between anorexia and high physical activity. “We know that people with anorexia have a really hard time sitting still,” says Bulik. Doctors had tended to think that this was a psychological symptom – that those individuals were still trying to lose weight. But this study suggests there is some genetic drive to move, says Bulik.
The team also found correlations with BMI, body fat, insulin resistance and levels of HDL cholesterol, which is known as “good cholesterol”. “Those things combined suggest that anorexia nervosa seems to be both a psychiatric and a metabolic disorder,” says Gerome Breen at King’s College, London, who worked with Bulik on the study.
Part of the puzzle
“It’s a very exciting advance in our understanding of the genetics of the disorder,” says Dolores Malaspina at the Icahn School of Medicine at Mount Sinai in New York. “It may suggest other ways beyond psychological ones to help people gain weight.”
But Malaspina cautions that the latest genetic clues are only a small part of the puzzle of anorexia. “The benefit of a large study sample size is that you are more likely to find a common genetic variant, but the trade-off is that it explains a smaller piece of any individual’s picture,” she says.
Given the complexity of the condition, there are likely to be varying subtypes – some people may have more of a psychiatric condition while others might have more of a metabolic type, says Bulik. She hopes that, in the future, genetic tests might diagnose a subtype, and help tailor a person’s treatment.
Bulik also hopes that the findings will help to reduce the stigma and misunderstanding of anorexia. Family doctors can still blame the parents of someone with the condition, or accuse girls with anorexia of being vain and wanting to look like models, she says. And even today, boys and men are told they can’t have anorexia, because it is a “girl’s disorder”, she says.
“I hope this changes the way people think about this illness,” says Bulik. “We are on a path to reconceptualising anorexia.”
Journal reference: Nature Genetics, DOI: 10.1038/s41588-019-0439-2
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