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OBJECTIVE: Night eating syndrome (NES) is an eating disorder characterized by evening hyperphagia. Despite having a prevalence comparable to some other eating disorders, NES remains sparsely investigated and poorly characterized. The present study examined the phenotypic and genetic associations for NES in the clinical Mass General Brigham Biobank.METHOD: Cases of NES were identified through relevant billing codes for eating disorders (F50.89/F50.9) and subsequent chart review; patients likely without NES were set as controls. Other diagnoses were determined from billing codes and collapsed into one of 1,857 distinct phenotypes based on clinical similarity. NES associations with diagnoses were systematically conducted in phenome-wide association scans using logistic regression models with adjustments for age, sex, race, and ethnicity. Polygenic scores for six related traits, namely for anorexia nervosa, depression, insomnia, sleep apnea, obesity, and type 2 diabetes were tested for associations with NES among participants of European ancestry using adjusted logistic regression models.RESULTS: Phenome-wide scans comparing patients with NES against controls (cases n = 88; controls n = 64,539) identified associations with 159 clinical diagnoses spanning 13 broad disease groups including endocrine/metabolic and digestive diseases. Notable associations were evident for bariatric surgery, vitamin D deficiency, sleep disorders (sleep apnea, insomnia, and restless legs syndrome), and attention deficit hyperactivity disorder. The polygenic scores for insomnia and obesity were associated with higher odds of NES (insomnia: odds ratio [OR], 1.24; 95% CI, 1.07, 1.43; obesity: 1.98; 95% CI, 1.71, 2.28).DISCUSSION: Complementary phenome-wide and genetic exploratory analyses provided information on unique and shared features of NES, offering insights that may facilitate its precise definition, diagnosis, and the development of targeted therapeutic interventions.