Abstract

Background/objectivesThe mediating role of eating behaviors in genetic susceptibility to weight gain during mid-adult life is not fully understood. This longitudinal study aims to help us understand contributions of genetic susceptibility and appetite to weight gain.Subjects/methodsWe followed the body-mass index (BMI) trajectories of 2464 adults from 45 to 65 years of age by measuring weight and height on four occasions at 5-year intervals. Genetic risk of obesity (gene risk score: GRS) was ascertained, comprising 92 BMI-associated single-nucleotide polymorphisms and split at a median (=high and low risk). At the baseline, the Eating Inventory was used to assess appetite-related traits of ‘disinhibition’, indicative of opportunistic eating or overeating and ‘hunger’ which is susceptibility to/ability to cope with the sensation of hunger. Roles of the GRS and two appetite-related scores for BMI trajectories were examined using a mixed model adjusted for the cohort effect and sex.ResultsDisinhibition was associated with higher BMI (β = 2.96; 95% CI: 2.66–3.25 kg/m2), and accounted for 34% of the genetically-linked BMI difference at age 45. Hunger was also associated with higher BMI (β = 1.20; 0.82–1.59 kg/m2) during mid-life and slightly steeper weight gain, but did not attenuate the effect of disinhibition.ConclusionsAppetite disinhibition is most likely to be a defining characteristic of genetic susceptibility to obesity. High levels of appetite disinhibition, rather than hunger, may underlie genetic vulnerability to obesogenic environments in two-thirds of the population of European ancestry.

Highlights

  • Obesity is a global health problem [1, 2] and the modern environment contributes importantly to this epidemic [3,4,5]

  • It is not known whether genetic risk of weight gain continues to operate via appetite mechanisms during adulthood because there are no longitudinal studies of genetic risk and appetite-related phenotypes

  • We examined clinically assessed body-mass index (BMI) trajectories in men and women from age 45 to 65 with the UK civil service, i.e., Whitehall II cohort according to gene risk score, and two appetite-related traits, using a multi-item eating behavior questionnaire [20]

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Summary

Introduction

Obesity is a global health problem [1, 2] and the modern environment contributes importantly to this epidemic [3,4,5]. Extended author information available on the last page of the article many adiposity-associated genetic variants have been identified [7]. In adults, elevated genetic risk of obesity is associated with appetite, blunted satiety [15], and high responsiveness to external food cues [16,17,18,19]. It is not known whether genetic risk of weight gain continues to operate via appetite mechanisms during adulthood because there are no longitudinal studies of genetic risk and appetite-related phenotypes

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