ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: This genome-wide association study (GWAS) of 16,992 cases of anorexia nervosa and 55 525 controls identified 8 significant loci. The findings show that the genetic architecture of anorexia nervosa mirrors its clinical features, showing significant genetic correlations with psychiatric disorders (obsessive-compulsive disorder, depression, anxiety, and schizophrenia), physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with BMI.

A previous smaller GWAS (3495 cases, 10 982 controls) estimated the common genetic variant-based heritability of anorexia nervosa to be ˜20%. This new GWAS suggests that anorexia nervosa is at least partly a metabolic disorder, and not purely psychiatric as previously thought. 36 genes were predicted to be differentially expressed in tissues or blood, and 4 variants were confirmed by expression analyses, chromatin interaction studies or both. These were the locus-intersecting genes CADM1 (Cell-adhesion molecule 1), MGMT (Methylguanin-DNA methyltransferase), FOXP1 (Forkhead box P1) and PTBP2 (Polypyrimidine tract-binding protein). The expression of MGMT, involved in a protein network related to brain tumors, was predicted to be downregulated in anorexia nervosa.

It was believed that metabolic abnormalities seen in individuals with anorexia nervosa are secondary to starvation and weight loss. Instead, this study shows that metabolic differences may be related to susceptibility to anorexia nervosa. The authors estimate that the metabolic factors may play nearly or as strong a role as psychiatric determinants in the development of anorexia nervosa. They conclude that anorexia nervosa should be thought of as a hybrid ‘metabo-psychiatric disorder’, and that it will be important to consider both metabolic and psychological factors when exploring new avenues for treating this potentially lethal illness.