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American Journal of Clinical Nutrition, Vol. 80, No. 6, 1478-1486, December 2004
© 2004 American Society for Clinical Nutrition


ORIGINAL RESEARCH COMMUNICATION

Neuromedin ß: a strong candidate gene linking eating behaviors and susceptibility to obesity1,2,3

Luigi Bouchard, Vicky Drapeau, Véronique Provencher, Simone Lemieux, Yvon Chagnon, Treva Rice, DC Rao, Marie-Claude Vohl, Angelo Tremblay, Claude Bouchard and Louis Pérusse

1 From the Division of Kinesiology, Department of Social and Preventive Medicine, Faculty of Medicine (LB, VD, AT, and LP), the Lipid Research Centre and the Department of Food Science and Nutrition (VP, SL, and M-CV), and the Psychiatric Genetic Unit, Robert-Giffard Research Center (YC), Laval University, Ste-Foy, Canada; the Division of Biostatistics (TR and DCR) and the Department of Genetics and Psychiatry (DCR), Washington University, School of Medicine, St Louis; and Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA (CB)

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 Québec 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 ß (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.

Key Words: Cognitive dietary restraint • disinhibition • susceptibility to hunger • behavioral genetics • Three-Factor Eating Questionnaire • quantitative trait locus




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