2010). It has been shown to be coregulated in the same gene network with proopiomelanocortin gene (POMC), one of the most important genes controlling metabolism, highlighting its potential role in food intake (Higgins et al. 2010). POMC is a central player of the melanocortin system within the arcuate nucleus of

the hypothalamus (reviewed in Cone 2006). Higgins et al. Inhibitors,research,lifescience,medical (2010) described a reduced POMC expression in fasted chicks. The coregulation of GRM8 and POMC suggests that glutamatergic neurotransmission may influence feeding behavior in chicks (Higgins et al. 2010). Glutamate itself is involved in addiction and may also influence food intake (Stanley et al. 1993). Furthermore, it has been postulated that common hedonic mechanisms may underlie obesity and drug addiction (Johnson and

Kenny 2010). Filbey et al. (2012) reported further indications Inhibitors,research,lifescience,medical for a potential overlap of neural mechanisms in addiction and compulsive overeating adding further weight on possibly common regulatory processes. In the present study we therefore hypothesized that rs2237781 within GRM8 might influence human eating behavior factors in a similar fashion as seen in smoking behavior. Using linear regression models we observed in the Sorbs significantly increased restraint scores in individuals for the homozygous major G allele for rs2237781. Restraint eating is Inhibitors,research,lifescience,medical known to be a behavioral trait check details cognitively controlling body weight not only in normal weight individuals but also in obese and overweight subjects. Individuals representing restraint eating behavior tend to rigorously Inhibitors,research,lifescience,medical control, for example, the amount of food intake as well as caloric intake. This may also serve as a counteracting behavior in order to attenuate the effects from frequent disinhibited eating. Thus, as both restraint and disinhibition are associated with increased body weight the restraint eating periods might fail resulting in disinhibited eating episodes which

would ultimately lead to higher BMI (Gallant et al. 2010). Further, it has to be mentioned that albeit not significant, we detected higher intake of of consumer goods such as alcohol, coffee, Inhibitors,research,lifescience,medical and cigarette smoking in homozygous G allele carriers in our discovery cohort. Our data prompted us to replicate the finding in two other independent cohorts, the German cohort and the Old Order Amish population. We identified in both populations the same effect direction as in the Sorbs but did not reach statistical significance which might most likely be due to low sample size. A weighted meta-analysis of all three cohorts revealed nominal associations of rs2237781 with increased restraint scores implying the variant might be involved in restraint eating to some extent. However, our data need to be interpreted with caution and can be viewed as a suggestive indication that rs2237781 may play a role in influencing restraint scores, especially in our discovery cohort.