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


METHODS
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).


CONCLUSIONS
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.
Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Clinical Research Department, Centre for Addiction and Mental Health, Toronto, Canada.
Zeynep
Z
Yilmaz
Clinical Research Department, Centre for Addiction and Mental Health, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada.
Allan S
AS
Kaplan
Neurogenetics Section, Centre for Addiction and Mental Health, Toronto, Canada.
Arun K
AK
Tiwari
Institute of Medical Science, University of Toronto, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada; Mood and Anxiety Program, Centre for Addiction and Mental Health, Toronto, Canada.
Robert D
RD
Levitan
Faculty of Medicine, University of Ottawa, Ottawa, Canada.
Sara
S
Piran
Center for Health Sciences, SRI International, Menlo Park, CA, USA.
Andrew W
AW
Bergen
Department of Psychiatry, University of California, San Diego, CA, USA.
Walter H
WH
Kaye
Joseph Stokes Jr. Research Institute, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Hakon
H
Hakonarson
Department of Psychiatry, University of Southern California, Los Angeles, CA, USA.
Kai
K
Wang
Department of Psychiatry, Center of Neurobiology and Behavior, University of Pennsylvania, Philadelphia, PA, USA.
Wade H
WH
Berrettini
Department of Psychiatry, Sheppard Pratt Health System, Towson, MD, USA.
Harry A
HA
Brandt
Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Cynthia M
CM
Bulik
Department of Psychiatry, Sheppard Pratt Health System, Towson, MD, USA.
Steven
S
Crawford
Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA.
Scott
S
Crow
Department of Psychiatry, University of Munich (LMU), Munich, Germany; Roseneck Hospital for Behavioral Medicine, Prien, Germany.
Manfred M
MM
Fichter
Department of Psychiatry, Weill Cornell Medical College, New York, NY, USA.
Katherine A
KA
Halmi
Eating Recovery Center, Denver, CO, USA.
Craig L
CL
Johnson
Department of Psychology, Florida State University, Tallahassee, FL, USA.
Pamela K
PK
Keel
Department of Psychology, Michigan State University, East Lansing, MI, USA.
Kelly L
KL
Klump
Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Pierre
P
Magistretti
Department of Clinical Neuroscience, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND, USA; Neuropsychiatric Research Institute, Fargo, ND, USA.
James E
JE
Mitchell
Department of Psychiatry, Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Michael
M
Strober
Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Laura M
LM
Thornton
Department of Academic Psychiatry, King's College London, Institute of Psychiatry, London, United Kingdom.
Janet
J
Treasure
Department of Psychiatry, University of Toronto, Toronto, Canada; Eating Disorders Program, Toronto General Hospital, Toronto, Canada.
D Blake
DB
Woodside
Institute of Medical Science, University of Toronto, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada; Neurogenetics Section, Centre for Addiction and Mental Health, Toronto, Canada.
Joanne
J
Knight
Institute of Medical Science, University of Toronto, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada; Neurogenetics Section, Centre for Addiction and Mental Health, Toronto, Canada. Electronic address: james_kennedy@camh.net.
James L
JL
Kennedy
D000328:Adult; D054369:Agouti-Related Protein / Q000235:genetics; D000856:Anorexia Nervosa / Q000235:genetics* / Q000503:physiopathology; D015992:Body Mass Index; D001835:Body Weight / Q000235:genetics*; D052018:Bulimia Nervosa / Q000235:genetics* / Q000503:physiopathology; D016022:Case-Control Studies; D005260:Female; D060005:Genotyping Techniques; D006801:Humans; D020738:Leptin / Q000235:genetics*; D053486:Melanocortins / Q000235:genetics*; D008562:Membrane Glycoproteins; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011494:Protein Kinases / Q000235:genetics; D011505:Protein-Tyrosine Kinases; D020813:Receptor, trkB
C515198:AGRP protein, human; D054369:Agouti-Related Protein; D020738:Leptin; D053486:Melanocortins; D008562:Membrane Glycoproteins; D009414:Nerve Growth Factors; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D020813:Receptor, trkB; C000591259:tropomyosin-related kinase-B, human
Anorexia nervosa; Body weight; Bulimia nervosa; Candidate gene association; Melanocortins; Neurotrophins