Genetic susceptibility to obesity mediated through eating behaviours

Abstract

The mechanisms underlying genetic risk to obesity remain unclear, including the degree to which sub-types of eating behaviours (e.g. disinhibition and rigid/flexible restraint) explain or alter the effect of polygenic risk for body mass index (BMI). Among >9,500 participants in the South-West of England, we observe BMI trajectory and rate of BMI change begins to differentiate by level of genetic risk to obesity from early infancy and continues into early adulthood. Mediation analyses reveal predisposition to higher BMI was partly mediated by eating behaviours (e.g. increased disinhibition, emotional eating and susceptibility to hunger) in adulthood. Furthermore, eating due to negative emotions during adolescence partly mediates genetic risk to obesity and adult emotional and disinhibited eating. For the first time we analyse the moderating influence of restraint subscales on the genetic susceptibility to obesity. We discovered that rigid or flexible restraint may ‘counter’ predisposition to higher BMI that is mediated via disinhibition and hunger. Lastly, to explore the intermediate phenotypes associated with genetic risk to obesity and eating behaviours, we examined Structural Magnetic Resonance Imaging data in 313 participants. Data suggest there was no mediation pathway between genetic risk, brain structure and eating behaviours tested in previous analyses. However, there were direct associations between BMI-genetic risk score and reduced structural measures taken from frontal lobe regions, and prefrontal cortex region reductions with restraint. We theorise that high genetic risk to obesity and loss of PFC integrity may negatively impact executive function, thus increase in eating behaviours such as disinhibition. and subsequent weight gain. These results suggest that improved management of disinhibited or emotional eating may reduce obesity risk among predisposed individuals and emphasise the potential need to intervene on eating behaviours during adolescence or earlier. We suggest restraint (any type) as a behaviour which could attenuate the indirect influence of high genetic risk to obesity. Application of this research could contribute to personalised interventions targeting specific genetic and eating behaviour profiles.