Anorexia Nervosa study with SNP/CNV Genotypes (NGS) data on dbGaP (93 participants)

phs001414 — Genetics of Eating Disorders

<p>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&#x3C;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.<br></p>