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

• Published in: The American journal of clinical nutrition Vol. 80; no. 6; pp. 1478 - 1486
• Main Authors: Bouchard, L, Drapeau, V, Provencher, V, Lemieux, S, Chagnon, Y, Rice, T, Rao, D.C, Vohl, M.C, Tremblay, A, Bouchard, C
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Clinical Nutrition 01.12.2004; American Society for Clinical Nutrition, Inc
• Subjects: adiposity; Adult; adults; analogs & derivatives; Analysis of Variance; Behavior; Biological and medical sciences; Chromosome Mapping; Chromosomes, Human, Pair 15; Chromosomes, Human, Pair 15 - genetics; Eating; Eating - genetics; eating habits; Feeding and Eating Disorders; Feeding and Eating Disorders - genetics; Female; Follow-Up Studies; Genes; Genetic Linkage; Genetic Markers; Genetic Predisposition to Disease; genetics; Genotype; human genetics; Humans; Hunger; hunger susceptibility; linkage (genetics); Male; Medical sciences; Metabolic diseases; missense mutation; Mutation, Missense; Neurokinin B; Neurokinin B - analogs & derivatives; Neurokinin B - genetics; neuromedin beta; NMB gene; Obesity; Obesity - genetics; peptide hormones; phenotype; Prospective Studies; Quantitative Trait Loci; Quebec; Quebec Family Study; Surveys and Questionnaires; Three-Factor Eating Questionnaire; Quebec; Human; Obesity; Feeding behavior; Questionnaire; susceptibility to hunger; Nutrition disorder; Three-Factor Eating Questionnaire; Cognitive dietary restraint; Genetic determinism; Hunger; Sensitivity; behavioral genetics; quantitative trait locus; Candidate gene; Locus; Nutritional status; disinhibition
• ISSN: 0002-9165; 1938-3207
• DOI: 10.1093/ajcn/80.6.1478

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.