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.]]>
Patients with a known or suspected history of an eating disorder, including Anorexia Nervosa, Bulimia Nervosa, Binge Eating Disorder, or Eating Disorder Not Otherwise Specified (EDNOS), are recruited to participate in the study. Inclusion Criteria: DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision) primary diagnosis of Anorexia Nervosa, Bulimia Nervosa, Binge Eating Disorder, or EDNOS, based on psychiatric interview and semi-structured interview Structured Clinical Interview for DSM (adolescents and adults) Age 14-70 years of age Males and Females All races and ethnicities Must be judged clinically stable by study investigators Outpatient, inpatient, or partial hospitalization patients Capable of providing informed assent/consent, in addition to parent/guardian consent when applicable Exclusion Criteria: Primary psychiatric diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder, mental retardation, pervasive developmental disorder, somatoform disorder, dissociative disorder, or posttraumatic stress disorder Active substance dependence (except nicotine) in the past 12 months Unstable medical illness History of seizures, serious head injury, concussions, or diagnosis of an organize brain disease Unable to read, speak, and understand EnglishAdditionally, we will ask unaffected family members to agree to participate in the study when 2 or more family members affected by eating disorders have enrolled in the study. ]]>
Phase 1: whole exome sequencing (WES) in 93 individuals with eating disorders]]>