Genes linked to psychiatric disorders and control of the body’s sugar and fat stores have been tied to anorexia in the largest ever study of the genetics of the devastating eating disorder.
The study looked at the genomes of nearly 17,000 people of European ancestry with anorexia, which has the highest death rate of any mental illness. It compared their genetic makeup to more than 55,000 people without the disorder.
Led by Cynthia Bulik, from the University of North Carolina at Chapel Hill, US, the researchers discovered eight genetic locations associated with the disease, some with links to over 100 genes expressed in the brain.
“Genes associated with anorexia nervosa were enriched for expression in most brain tissues,” the authors write.
One such region, the hippocampus, plays a big role in the feeding behaviour of mice, including food motivation and reward, the authors note.
The vast genetic database allowed the researchers to test whether a genetic signature of anorexia overlapped with those of other psychological disorders or metabolic changes.
Anorexia, which affects around one in 200 people, mainly girls and young women, was found to be strongly linked to obsessive compulsive disorder and to have weaker but significant links with depression, schizophrenia and anxiety.
The researchers also found positive correlations with years of education, college completion and, consistent with a common trait in the disorder, levels of physical activity.
But there were also links to two of the body’s most important hormones involved in hunger and blood sugar control; leptin, which induces a feeling of fullness after eating, and insulin, which brings down sugar levels.
The findings could re-draft the road map for how anorexia is treated which, the authors point out, is in something of a rut.
“Low BMI has traditionally been viewed as a consequence of the psychological features of anorexia nervosa (that is, drive for thinness and body dissatisfaction). This perspective has failed to yield interventions that reliably lead to sustained weight gain and psychological recovery,” they write.
Indeed, the mortality rates for anorexia make shocking reading. The death rate for the almost exclusively female illness (the study included nearly 15,000 females but just 447 males) is 20% over 20 years.
The findings lead the authors to call for a frame shift in our approach to anorexia.
“Fundamental metabolic dysregulation may contribute to the exceptional difficulty that individuals with anorexia nervosa have in maintaining a healthy BMI (even after therapeutic renourishment),” they write.
“Our results encourage consideration of both metabolic and psychological drivers of anorexia nervosa when exploring new avenues for treating this frequently lethal illness,” the authors conclude.
The study appears in the journal Nature Genetics.