title: Opioid receptor mu 1 gene, fat intake and obesity in adolescence.
abstract: Dietary preference for fat may increase risk for obesity. It is a complex behavior regulated in part by the amygdala, a brain structure involved in reward processing and food behavior, and modulated by genetic factors. Here, we conducted a genome-wide association study (GWAS) to search for gene loci associated with dietary intake of fat, and we tested whether these loci are also associated with adiposity and amygdala volume. We studied 598 adolescents (12-18 years) recruited from the French-Canadian founder population and genotyped them with 530 011 single-nucleotide polymorphisms. Fat intake was assessed with a 24-hour food recall. Adiposity was examined with anthropometry and bioimpedance. Amygdala volume was measured by magnetic resonance imaging. GWAS identified a locus of fat intake in the μ-opioid receptor gene (OPRM1, rs2281617, P=5.2 × 10(-6)), which encodes a receptor expressed in the brain-reward system and shown previously to modulate fat preference in animals. The minor OPRM1 allele appeared to have a 'protective' effect: it was associated with lower fat intake (by 4%) and lower body-fat mass (by ∼2 kg, P=0.02). Consistent with the possible amygdala-mediated inhibition of fat preference, this allele was additionally associated with higher amygdala volume (by 69 mm(3), P=0.02) and, in the carriers of this allele, amygdala volume correlated inversely with fat intake (P=0.02). Finally, OPRM1 was associated with fat intake in an independent sample of 490 young adults. In summary, OPRM1 may modulate dietary intake of fat and hence risk for obesity, and this effect may be modulated by subtle variations in the amygdala volume.
authors: The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors: A
authors: A
authors: Haghighi
authors: The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors: M G
authors: MG
authors: Melka
authors: The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors: M
authors: M
authors: Bernard
authors: Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada.
authors: M
authors: M
authors: Abrahamowicz
authors: Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
authors: G T
authors: GT
authors: Leonard
authors: Department of Psychology, Université du Québec à Chicoutimi, Chicoutimi, Quebec, Canada.
authors: L
authors: L
authors: Richer
authors: 1] ÉCOBES, Recherche et transfert, Cégep de Jonquière, Jonquière, Quebec, Canada [2] Department of Human Sciences, Université du Québec à Chicoutimi, Chicoutimi, Quebec, Canada.
authors: M
authors: M
authors: Perron
authors: 1] ÉCOBES, Recherche et transfert, Cégep de Jonquière, Jonquière, Quebec, Canada [2] Department of Human Sciences, Université du Québec à Chicoutimi, Chicoutimi, Quebec, Canada.
authors: S
authors: S
authors: Veillette
authors: Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada.
authors: C J
authors: CJ
authors: Xu
authors: Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada.
authors: C M T
authors: CM
authors: Greenwood
authors: Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada.
authors: A
authors: A
authors: Dias
authors: Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada.
authors: A
authors: A
authors: El-Sohemy
authors: Community Genomic Centre, Université de Montréal, Chicoutimi Hospital, Chicoutimi, Quebec, Canada.
authors: D
authors: D
authors: Gaudet
authors: 1] Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada [2] Rotman Research Institute, University of Toronto, Toronto, Ontario, Canada.
authors: T
authors: T
authors: Paus
authors: The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors: Z
authors: Z
authors: Pausova
mesh_terms: D050154:Adiposity / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000679:Amygdala / Q000378:metabolism / Q000473:pathology; D015992:Body Mass Index; D002170:Canada; D002648:Child; D003430:Cross-Sectional Studies; D004041:Dietary Fats / Q000009:adverse effects*; D002149:Energy Intake / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D009765:Obesity / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017450:Receptors, Opioid, mu / Q000235:genetics*; D055815:Young Adult
chemical_list: D004041:Dietary Fats; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu