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

Am J Clin Nutr. 2004 Dec;80(6):1478-86. doi: 10.1093/ajcn/80.6.1478.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analysis of Variance
  • Chromosome Mapping
  • Chromosomes, Human, Pair 15 / genetics*
  • Eating / genetics*
  • Feeding and Eating Disorders / genetics*
  • Female
  • Follow-Up Studies
  • Genetic Linkage*
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Hunger
  • Male
  • Mutation, Missense
  • Neurokinin B / analogs & derivatives*
  • Neurokinin B / genetics*
  • Obesity / genetics*
  • Prospective Studies
  • Quantitative Trait Loci
  • Quebec
  • Surveys and Questionnaires

Substances

  • Genetic Markers
  • Neurokinin B
  • neuromedin B