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Opioid receptor mu 1 gene, fat intake and obesity in adolescence

Molecular Psychiatry volume 19, pages 63–68 (2014)Cite this article

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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 mm3, 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.

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Acknowledgements

We thank the following individuals for their contributions in acquiring data: Jacynthe Tremblay and her team of research nurses (Saguenay Hospital), Helene Simard and her team of research assistants (Cégep de Jonquière) and Dr Rosanne Aleong (program manager, Rotman Research Institute). The Canadian Institutes of Health Research (ZP, TP) funds the SYS. MA is a James McGill Professor of Biostatistics at McGill University. TP is the Tanenbaum Chair in Population Neuroscience at the Rotman Research Institute, University of Toronto.

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Authors and Affiliations

  1. The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada

    A Haghighi, M G Melka, M Bernard & Z Pausova

  2. Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada

    M Abrahamowicz, C J Xu & C M T Greenwood

  3. Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada

    G T Leonard & T Paus

  4. Department of Psychology, Université du Québec à Chicoutimi, Chicoutimi, Quebec, Canada

    L Richer

  5. ÉCOBES, Recherche et transfert, Cégep de Jonquière, Jonquière, Quebec, Canada

    M Perron & S Veillette

  6. Department of Human Sciences, Université du Québec à Chicoutimi, Chicoutimi, Quebec, Canada

    M Perron & S Veillette

  7. Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada

    A Dias & A El-Sohemy

  8. Community Genomic Centre, Université de Montréal, Chicoutimi Hospital, Chicoutimi, Quebec, Canada

    D Gaudet

  9. Rotman Research Institute, University of Toronto, Toronto, Ontario, Canada

    T Paus

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  1. A Haghighi
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Correspondence to Z Pausova.

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Haghighi, A., Melka, M., Bernard, M. et al. Opioid receptor mu 1 gene, fat intake and obesity in adolescence. Mol Psychiatry 19, 63–68 (2014). https://doi.org/10.1038/mp.2012.179

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