Binge eating disorder (BED) is the most common eating disorder and is associated with high mortality and morbidity. Despite its prevalence and severity, BED is under-researched, under-recognised, and under-treated. Dysregulated levels of appetite-regulating hormones (e.g., ghrelin, GHRL; glucagon-like peptide-1, GLP1) are putative risk factors for binge eating, a core feature of BED. These hormones may act via biological mechanisms – influencing brain regions involved in homeostatic regulation, reward processing, and inhibitory control – or environmental pathways – such as weight stigma linked to increased weight gain, and consequent cycles of restriction and binge eating. Drugs targeting these hormones, such as GLP1 receptor agonists (GLP1RAs, e.g., semaglutide), could hold potential as adjunct treatments for binge eating.
This project aims to understand the genetic and environmental causal determinants of binge eating, with a particular focus on appetite and its biological and environmental downstream mechanisms. This study aims to obtain novel mechanistic insights into binge eating risk, identify susceptible individuals, and establish preventative and therapeutic targets through analysis of risk factor associations using novel causal inference methodology. Causal inference methods such as PRS analysis, Mendelian randomization (MR) analyses will be used alongside traditional epidemiological methods such as moderation and mediation analyses. MR and PRS analyses will consider any potential risk factor, including (but not limited to) anthropometric (e.g., adiposity), social (e.g., weight-stigma), and molecular markers (e.g., metabolites, proteins). For example, we will use GRS for each drug target to assess whether the genetic relationship of appetite-regulating hormones with binge eating varies according to an individual’s genetic liability to higher weight.
