Neuromedin β:: a strong candidate gene linking eating behaviors and susceptibility to obesity

Background: Obesity is frequently associated with eating disorders, and evidence indicates that both conditions are influenced by genetic factors. However, little is known about the genes influencing eating behaviors. Objective: The objective was to identify genes associated with eating behaviors. Design: Three eating behaviors were assessed in 660 adults from the Quebec Family Study with the use of the Three-Factor Eating Questionnaire. A genome-wide scan was conducted with a total of 471 genetic markers spanning the 22 autosomes to identify quantitative trait loci for eating behaviors. Body composition and macronutrient and energy intakes were also measured. Results: Four quantitative trait loci were identified for disinhibition and susceptibility to hunger. Of these, the best evidence of linkage was found between a locus on chromosome 15q24-q25 and disinhibition (P < 0.0058) and susceptibility to hunger (P < 0.0001). After fine-mapping, the peak linkage was found between markers D 155206 and D 155201 surrounding the neuromedin beta (NMB) gene. A missense mutation (p.P737 located within the NMB gene showed significant associations with eating behaviors and obesity phenotypes. The T73T homozygotes were 2 times as likely to exhibit high levels of disinhibition (odds ratio: 1.8; 95% CI: 1.07, 2.89; P = 0.03) and susceptibility to hunger (odds ratio: 1.9; 95% CI: 1.15, 3.06; P = 0.01) as were the P73 allele carriers. Six-year follow-up data showed that the amount of body fat gain over time in T73T subjects was >2 times that than in P73P homozygotes (3.6 compared with 1.5 kg; P < 0.05). Conclusion: The results suggest that NMB is a very strong candidate gene of eating behaviors and predisposition to obesity.