J Psychiatry Neurosci 2015;40(1):38-45
Ken W.K. Lee, MSc; Michal Abrahamowicz, PhD; Gabriel T. Leonard, PhD; Louis Richer, PhD; Michel Perron, PhD; Suzanne Veillette, PhD; Eva Reischl, PhD; Luigi Bouchard PhD; Daniel Gaudet, MD, PhD; Tomas Paus, MD, PhD; Zdenka Pausova, MD
Background: Preference for fatty foods is a risk factor for obesity. It is a complex behaviour that involves the brain reward system and is regulated by genetic and environmental factors, such as the opioid receptor mu-1 gene (OPRM1) and prenatal exposure to maternal cigarette smoking (PEMCS). We examined whether OPRM1 and PEMCS interact in influencing fat intake and whether exposure-associated epigenetic modifications of OPRM1 may mediate this gene–environment interaction.
Methods: We studied adolescents from a French Canadian genetic founder population, half of whom were exposed prenatally to maternal cigarette smoking. Fat intake was assessed with a 24-hour food recall in the form of a structured interview conducted by a trained nutritionist. The OPRM1 variant rs2281617 was genotyped for the whole sample with the Illumina Human610-Quad and HumanOmniExpress BeadChips. Methylation of blood DNA was assessed at 21 CpGs across OPRM1 in a subset of the sample using the Illumina HumanMethylation450 BeadChip.
Results: We included 956 adolescents in our study. In the whole sample, OPRM1 (T carrier in rs2281617) was associated with lower fat intake (–1.6%, p = 0.017), and PEMCS was associated with higher fat intake (+1.6%, p = 0.005). OPRM1 and PEMCS interacted with each other (p = 0.003); the “protective” (fat intake–lowering) allele of OPRM1 was associated with lower fat intake in nonexposed (–3.2%, p < 0.001) but not in exposed individuals (+0.8%, p = 0.42). Further, PEMCS was associated with lower DNA methylation across multiple CpGs across OPRM1 in exposed versus nonexposed individuals (p = 0.031).
Limitations: A limitation of our study was its cross-sectional design.
Conclusion: Our study suggests that PEMCS may interact with OPRM1 in increasing fat preference. Silencing of the protective OPRM1 allele in exposed adolescents might be related to epigenetic modification of this gene.
Submitted Nov. 19, 2013; Revised Jan. 26, Apr. 20, 2014; Accepted May 13, 2014; Early-released Aug. 19, 2014.
Acknowledgments: The authors thank Ms. Celine Bourdon for her contribution to statistical analyses. The Canadian Institutes of Health Research (D. Gaudet, T. Paus, Z. Pausova) funds the Saguenay Youth Study. The McLaughlin Centre at the University of Toronto (L. Bouchard, T. Paus, Z. Pausova) funds the DNA methylation study. M. Abrahamowicz is a James McGill Professor of Biostatistics at McGill University. T. Paus is the Tanenbaum Chair in Population Neuroscience at the Rotman Research Institute, University of Toronto.
Affiliations: Hospital for Sick Children, University of Toronto, Toronto, Ont., Canada (Lee, Pausova); Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal, Que., Canada (Abrahamowicz); Montreal Neurological Institute, McGill University, Montréal, Que., Canada (Leonard); Department of Psychology (Richer), Department of Human Sciences (Perron, Veillette), Université du Québec à Chicoutimi, Que., Canada; ÉCOBES, Recherche et transfert, Cégep de Jonquière, Jonquière, Que., Canada (Perron, Veillette); Research Unit of Molecular Epidemiology, Helmholtz Zentrum Munchen, Munich, Germany (Reischl); Department of Biochemistry, Université de Sherbrooke, Sherbrooke, Que., Canada (Bouchard); ECOGENE-21 and Lipid Clinic, Chicoutimi Hospital, Chicoutimi, Que., Canada (Bouchard, Gaudet); Community Genomic Centre, Université de Montréal, Chicoutimi Hospital, Chicoutimi, Que., Canada (Gaudet); Rotman Research Institute, University of Toronto, Toronto, Ont., Canada (Paus).
Competing interests: None declared.
Contributors: Z. Pausova designed the study. G.T. Leonard, L. Richer, M. Perron, S. Veillette, E. Reischl, D. Gaudet, T. Paus and Z. Pausova acquired the data, which K.W.K. Lee, M. Abrahamowicz, L. Bouchard, T. Paus and Z. Pausova analyzed. K.W.K. Lee and Z. Pausova wrote the article, which all authors reviewed and approved for publication.
Correspondence to: Z. Pausova, Peter Gilgan Centre for Research and Learning, 686 Bay St., 10–9705, Toronto ON M5G 0A4; firstname.lastname@example.org