Approved research

Role of lifestyle-related behaviors in mediating genetic susceptibility to obesity

Lay summary

The dramatic increase in the prevalence of obesity observed worldwide is largely explained by changes in our lifestyle (unhealthy eating habits, reduced physical activity level, increased sedentary behaviors) and our environment (food supply, social and physical environments). Understanding how lifestyle-related behaviors interact with genetic factors to lead to obesity is important to improve the prevention and treatment of obesity. The objective of this research project is to investigate the role of various lifestyle-related behaviors (diet, physical activity, sedentary behavior, sleeping) in mediating the relationship between genetic susceptibility to obesity (assessed with genetic risk score based on genetic variants previously shown to be associated with obesity) and various obesity traits. The goal of mediation analyses is to identify the pathways (mediators) whereby an exposure (genetic susceptibility) leads to an outcome (obesity). This is in contrast to the effect modification approach used traditionally in genetic studies to provide evidence of gene-environment interaction, which is based on the observation that the effect of the exposure on the outcome is modified by an environmental factor, for example physical activity. Although the concepts of mediation and effect modification are interdependent, their clinical applicability differ. Assessing interaction may help identify subset of individuals who would benefit (or not) from an intervention, while assessing mediation allows the identification of behaviors one might intervene on to lessen the risk of obesity and/or to improve management and treatment of obesity. Our rationale is that by identifying the lifestyle-related behaviors mediating genetic susceptibility to obesity, we will improve our understanding of the pathways leading to obesity in high-risk individuals, which could lead to the development of new strategies to better prevent and treat obesity. The estimated duration of the project is 3 years. The proposed research fits with the aims of the UK Biobank to improve the prevention, diagnosis and treatment of a wide range of chronic diseases.