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Mediation and modification of genetic susceptibility to obesity by eating behaviors.

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de Lauzon-Guillain, Blandine  ORCID logo
Clément, Karine 


Background: Many genetic variants show highly robust associations with body mass index (BMI). However, the mechanisms through which genetic susceptibility to obesity operates are not well understood. Potentially modifiable mechanisms, including eating behaviors, are of particular interest to public health.Objective: Here we explore whether eating behaviors mediate or modify genetic susceptibility to obesity.Design: Genetic risk scores for BMI (BMI-GRSs) were calculated for 3515 and 2154 adults in the Fenland and EDEN (Etude des déterminants pré et postnatals de la santé et du développement de l'enfant) population-based cohort studies, respectively. The eating behaviors-emotional eating, uncontrolled eating, and cognitive restraint-were measured through the use of a validated questionnaire. The mediating effect of each eating behavior on the association between the BMI-GRS and measured BMI was assessed by using the Sobel test. In addition, we tested for interactions between each eating behavior and the BMI-GRS on BMI.Results: The association between the BMI-GRS and BMI was mediated by both emotional eating (EDEN: P-Sobel = 0.01; Fenland: P-Sobel = 0.02) and uncontrolled eating (EDEN: P-Sobel = 0.04; Fenland: P-Sobel = 0.0006) in both sexes combined. Cognitive restraint did not mediate this association (P-Sobel > 0.10), except among EDEN women (P-Sobel = 0.0009). Cognitive restraint modified the relation between the BMI-GRS and BMI among men (EDEN: P-interaction = 0.0001; Fenland: P-interaction = 0.04) and Fenland women (P-interaction = 0.0004). By tertiles of cognitive restraint, the association between the BMI-GRS and BMI was strongest in the lowest tertile of cognitive restraint, and weakest in the highest tertile.Conclusions: Genetic susceptibility to obesity was partially mediated by the "appetitive" eating behavior traits (uncontrolled and emotional eating) and, in 3 of the 4 population groups studied, was modified by cognitive restraint. High levels of cognitive control over eating appear to attenuate the genetic susceptibility to obesity. Future research into interventions designed to support restraint may help to protect genetically susceptible individuals from weight gain.



BMI, body mass index, dieting, eating behavior, genetic risk score, genetics, obesity, Adult, Appetite, Body Mass Index, Cognition, Eating, Emotions, Feeding Behavior, Female, Gene-Environment Interaction, Genetic Predisposition to Disease, Humans, Hyperphagia, Male, Middle Aged, Obesity, Risk Factors, Self-Control, Sex Factors, Surveys and Questionnaires

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Am J Clin Nutr

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Elsevier BV
Medical Research Council (MC_UU_12015/1)
Medical Research Council (MC_UU_12015/5)
Medical Research Council (MC_UU_12015/3)
Medical Research Council (MC_UU_12015/2)
Medical Research Council (MC_UU_12015/4)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0512-10135)
MRC (MC_PC_13046)
MRC (MC_PC_13048)
Medical Research Council (MC_U106179473)
Medical Research Council (MC_U106179471)
The EDEN study is supported by: Fondation pour la Recherche Médicale (FRM), French Ministry of Research: Federative Research Institutes and Cohort Program, INSERM Human Nutrition National Research Program, and Diabetes National Research Program (through a collaboration with the French Association of Diabetic Patients (AFD)), French Ministry of Health, French Agency for Environment Security (AFSSET), French National Institute for Population Health Surveillance (InVS), Paris–Sud University, French National Institute for Health Education (INPES), Nestlé, Mutuelle Générale de l’Education Nationale (MGEN), French speaking association for the study of diabetes and metabolism (ALFEDIAM), National Agency for Research (ANR non thematic program), National Institute for Research in Public health (IRESP: TGIR cohorte santé 2008 program). The Fenland Study is supported by the Medical Research Council (MC_U106179471). This work was supported by the Medical Research Council [Unit Programme numbers MC_UU_12015/2 and MC_UU_12015/1]. Genotyping was supported by the Medical Research Council (MC_PC_13046). We are grateful to all the volunteers for their time and help and to the General Practitioners and practice staff for assistance with recruitment. We thank the Fenland Study Investigators, Fenland Study Co-ordination team and the Epidemiology Field, Anthropometry, Data and Laboratory teams. Biochemical assays were performed by the National Institute for Health Research, Cambridge Biomedical Research Centre, Core Biochemistry Assay Laboratory, and the Cambridge University Hospitals NHS Foundation Trust, Department of Clinical Biochemistry.