Genomics uncovers diverse biological backgrounds of eating disorders

While major eating disorders share common genetic psychiatric risk, the genetics of body weight regulation may predispose a person to develop a particular eating disorder over others, according to a new study.

“Here, we present the first molecular genetic evidence that the underlying biology differs between binge-type eating disorders, including bulimia nervosa and binge-eating disorder, and anorexia nervosa and these differences can be captured at the genomic level,” the researchers said.

Genome-wide polygenic scores were calculated for people with eating disorders and healthy controls, whose data were retrieved from the UK Biobank database. Each score considers risk genes for any particular trait. More than 250 scores were calculated for each participant, describing their genetic liability to various psychiatric, physical, and metabolic traits. Findings were replicated in the Avon Longitudinal Study of Parents and Children.

Looking at three major eating disorders (anorexia nervosa, bulimia nervosa, and binge-eating disorder), investigators found 18 polygenic risk scores that seemed significantly associated. [Int J Eat Disord 2021;doi:10.1002/eat.23481]

For example, the schizophrenia polygenic score was significantly and positively correlated with both anorexia nervosa (odds ratio [OR] per standard deviation in polygenic score, 1.18, 95 percent confidence interval [CI], 1.09–1.27) and binge-eating disorder (OR, 1.23, 95 percent CI, 1.13–1.35). Both eating disorders were significantly correlated with the polygenic score for major depressive disorder, too.

The liability to psychiatric traits did not significantly correlate with bulimia nervosa, though this could only be due to weak statistical power. Nevertheless, “the patterning of associations for the two binge-type eating disorders was comparable,” the researchers explained, referring to both bulimia nervosa and binge-eating disorder.

“[W]e discuss bulimia nervosa and binge-eating disorder grouped as binge-type eating disorders because they showed a similar pattern of associations with the polygenic scores, especially with reference to psychiatric/behavioural and anthropometric phenotypes,” they added.

In particular, the analysis of somatic traits revealed key differences between anorexia nervosa and the two binge-type eating disorders.

While binge-eating disorder was significantly associated with polygenic risk scores for childhood obesity (OR, 1.22, 95 percent CI, 1.12–1.33) and age at menarche (OR, 0.79, 95 percent CI, 0.72–0.86), anorexia was not. Instead, polygenic risk for adult obesity showed a stronger link to anorexia nervosa.

Both binge-type disorders—bulimia nervosa and binge-eating disorder—shared interactions with genetic liability to obesity and waist circumference. In addition, binge-eating disorder was also significantly correlated with the polygenic score for hip and waist circumference, obesity, and body mass index.

“Our findings show for the first time that similarities exist in the genomic psychiatric liability for binge-type eating disorders and anorexia nervosa,” the researchers said. “However, we find clear differences between binge-type eating disorders and anorexia nervosa in the underlying biology of body mass regulation at the genomic level.”

“These findings open important avenues for translational research relevant to eating disorder phenotypes and overlap between eating disorders,” they added.