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

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

Bibliographical note

Funding Information:
Dr. Kennedy has received honoraria from Eli Lilly and Roche, whereas Dr. Levitan has received honorarium from Astra-Zeneca. Dr. Bergen is an employee of SRI International, and has received research, salary and travel support from the National Institutes of Health, from the Price Foundation, Ltd., and from the University of California, San Diego, through grants, study section service, and through professional service agreements. Dr. Bulik is a consultant for Shire Pharmaceuticals. Other authors have no financial interests to disclose.

Funding Information:
The present study was funded by research grants from the Ontario Mental Health Foundation (awarded to Drs. Kaplan and Levitan) and Province of Ontario Academic Health Science Centres Academic Funding Plan Innovation Fund (awarded to Drs. Kaplan and Kennedy). Dr. Yilmaz was funded by a Canadian Institutes of Health Research Doctoral Research Award ( 200910GSD-248658-174637 ) and is currently supported by the National Institutes of Health (NIH) Grant T32MH076694 (PI: Bulik). Dr. Tiwari is supported by the Brain & Behavior Research Foundation Young Investigator Award. None of these funding agencies had any influence on the design or results of the study.


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


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