The role of leptin, melanocortin, and neurotrophin system genes on body weight in anorexia nervosa and bulimia nervosa

Zeynep Yilmaz, Allan S. Kaplan, Arun K. Tiwari, Robert D. Levitan, Sara Piran, Andrew W. Bergen, Walter H. Kaye, Hakon Hakonarson, Kai Wang, Wade H. Berrettini, Harry A. Brandt, Cynthia M. Bulik, Steven Crawford, Scott Crow, Manfred M. Fichter, Katherine A. Halmi, Craig L. Johnson, Pamela K. Keel, Kelly L. Klump, Pierre MagistrettiJames E. Mitchell, Michael Strober, Laura M. Thornton, Janet Treasure, D. Blake Woodside, Joanne Knight, James L. Kennedy*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Objective: Although low weight is a key factor contributing to the high mortality in anorexia nervosa (AN), it is unclear how AN patients sustain low weight compared with bulimia nervosa (BN) patients with similar psychopathology. Studies of genes involved in appetite and weight regulation in eating disorders have yielded variable findings, in part due to small sample size and clinical heterogeneity. This study: (1) assessed the role of leptin, melanocortin, and neurotrophin genetic variants in conferring risk for AN and BN; and (2) explored the involvement of these genes in body mass index (BMI) variations within AN and BN. Method: Our sample consisted of 745 individuals with AN without a history of BN, 245 individuals with BN without a history of AN, and 321 controls. We genotyped 20 markers with known or putative function among genes selected from leptin, melanocortin, and neurotrophin systems. Results: There were no significant differences in allele frequencies among individuals with AN, BN, and controls. AGRP rs13338499 polymorphism was associated with lowest illness-related BMI in those with AN (p=0.0013), and NTRK2 rs1042571 was associated with highest BMI in those with BN (p=0.0018). Discussion: To our knowledge, this is the first study to address the issue of clinical heterogeneity in eating disorder genetic research and to explore the role of known or putatively functional markers in genes regulating appetite and weight in individuals with AN and BN. If replicated, our results may serve as an important first step toward gaining a better understanding of weight regulation in eating disorders.

Original languageEnglish (US)
Pages (from-to)77-86
Number of pages10
JournalJournal of Psychiatric Research
Issue number1
StatePublished - 2014


  • Anorexia nervosa
  • Body weight
  • Bulimia nervosa
  • Candidate gene association
  • Melanocortins
  • Neurotrophins

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

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