Association between MC4R rs17782313 polymorphism and overeating behaviors

Abstract

Background/objectives: 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.

Subjects/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.

Conflict of interest statement

Conflict of Interest

Dr. Kennedy has received honoraria from Eli Lilly and Roche, whereas Dr. Levitan has received honorarium from Astra-Zeneca. Other authors have no financial interests to disclose.

Figures

Figure 1

Multiple mediation model of the relationship between MC4R, depressed mood, emotional eating/cravings, and BMI. Note. Standardized coefficients are presented and tested for significance with 95% confidence intervals calculated using the bias-corrected bootstrap method (5000 samples). a = standardized IV to Med coefficient, b = standardized Med to DV coefficient, c = standardized total effect (IV to DV), c′ = standardized direct effect. Subscripts refer to specific indirect paths. * p

Figure 2

Linkage disequilibrium plot for the five MC4R markers.