Association between MC4R rs17782313 polymorphism and overeating behaviors.
OBJECTIVE
Melanocortins have a crucial role in appetite and weight regulation. Although the melanocortin 4 receptor (MC4R) gene has been repeatedly linked to obesity and antipsychotic-induced weight gain, the mechanism behind how it leads to this effect in still undetermined. The goal of this study was to conduct an in-depth and sophisticated analysis of MC4R polymorphisms, body mass index (BMI), eating behavior and depressed mood.


METHODS
We genotyped 328 individuals of European ancestry on the following MC4R markers based on the relevant literature on obesity and antipsychotic-induced weight gain: rs571312, rs17782313, rs489693, rs11872992, and rs8087522. Height and weight were measured, and information on depressed mood and overeating behaviors was obtained during the in-person assessment.


RESULTS
BMI was associated with rs17782313 C allele; however, this finding did not survive correction for multiple testing (P = 0.018). Although rs17782313 was significantly associated with depressed mood and overeating behaviors, tests of indirect effects indicated that emotional eating and food cravings, rather than depressed mood, uniquely accounted for the effect of this marker and BMI (n = 152).


CONCLUSIONS
To our knowledge, this is the first study to investigate the link between MC4R rs17782313, mood and overeating behavior, as well as to demonstrate possible mechanisms behind MC4R's influence on body weight. If replicated in a larger sample, these results may have important clinical implications, including potential for the use of MC4R agonists in the treatment of obesity and disordered eating.
1] Department of Psychiatry, Center of Excellence for Eating Disorders, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA [2] Clinical Research Department, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
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Z
Yilmaz
1] Clinical Research Department, Centre for Addiction and Mental Health, Toronto, Ontario, Canada [2] Kinesiology and Health Sciences, York University, Toronto, Ontario, Canada [3] Eating Disorders Program, Toronto General Hospital, Toronto, Ontario, Canada.
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C
Davis
School of Psychology, The University of Queensland, Brisbane, Queensland, Australia.
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NJ
Loxton
1] Clinical Research Department, Centre for Addiction and Mental Health, Toronto, Ontario, Canada [2] Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada [3] Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
A S
AS
Kaplan
1] Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada [2] Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada [3] Mood and Anxiety Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
R D
RD
Levitan
Department of Psychology, Memorial University, St. John's, Newfoundland, Canada.
J C
JC
Carter
1] Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada [2] Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada [3] Neurogenetics Section, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
J L
JL
Kennedy
D000328:Adult; D000483:Alleles; D014150:Antipsychotic Agents / Q000009:adverse effects; D015992:Body Mass Index; D003863:Depression / Q000235:genetics; D005247:Feeding Behavior / Q000523:psychology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D006963:Hyperphagia / Q000235:genetics* / Q000523:psychology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics*; D012307:Risk Factors; D011795:Surveys and Questionnaires; D015430:Weight Gain / Q000235:genetics; D044465:White People / Q000235:genetics
D014150:Antipsychotic Agents; C470072:MC4R protein, human; D044105:Receptor, Melanocortin, Type 4