Eating disorders such as anorexia nervosa and bulimia nervosa are considered to be the result of genetic predisposition and environmental risk factors. Despite eating disorders being common to families, no definitive genetic basis for disease predisposition has been identified.

In this issue of the Journal of Clinical Investigation, Michael Lutter and colleagues at the University of Iowa identified genetic mutations in two separate families affected by eating disorders that were linked to the same transcriptional pathway.

The researchers determined that a mutation in the gene encoding the transcription factor estrogen-related receptor α (ERRSA) correlated with eating disorder development in one family and a mutation in gene encoding the transcriptional repressor histone deacetylase 4 (HDAC4) associated with eating disorders in the second family. The mutant forms of both ERRSA and HDAC4 resulted in reduced expression of known ERRSA-dependent genes.

These findings indicate that individuals with mutations that reduce ESRRA activity have an increased risk of developing eating disorders.