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Genetics of Eating Disorders

This genetic study examines Anorexia Nervosa, Bulimia Nervosa, and Binge Eating Disorder. We performed whole exome sequencing (WES) on 93 unrelated individuals with eating disorders (38 restricted-eating, 55 binge-eating) to identify novel damaging variants. Using an unbiased, data-driven approach, we prioritized candidate genes with an excessive burden of predicted damaging variants. We then empirically tested one top candidate pathway in a mouse model of binge-like eating. We identified an excess of novel damaging variants in 186 genes in the restricted-eating group and 245 genes in the binge-eating group. The list of genes significantly enriched (OR = 4.6, p<0.0001) for neuropeptide/neurotrophic pathways related to appetite regulation, including neurotensin, glucagon-like peptide 1, and BDNF signaling. Notably, administration of the glucagon-like peptide 1 receptor agonist exendin-4 significantly reduced food intake in a mouse model of 'binge-like' eating. These findings highlight the role of ultra-rare and novel damaging variants in neuropeptide/neurotropic factor signaling pathways in the development of eating disorder behaviors. They also suggest that glucagon-like peptide 1 receptor agonists may hold promise as a treatment for binge eating.