Am J Clin Nutr. 2004 Dec;80(6):1478-86.
Neuromedin beta: a strong candidate gene linking eating behaviors and susceptibility to obesity.
Bouchard L, Drapeau V, Provencher V, Lemieux S, Chagnon Y, Rice T, Rao DC, Vohl MC, Tremblay A, Bouchard C, Perusse L.
Division of Kinesiology, Department of Social and Preventive Medicine, Faculty of Medicine, Lipid Research Centre, Canada.
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 D15S206 and D15S201 surrounding the neuromedin beta (NMB) gene. A missense mutation (p.P73T) 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. |
