Monogenic obesity is caused by the dysfunction of genes involved in the satiety pathway. While the penetrance and modes of transmission of certain genes, such as MC4R, are well-established, others require further characterization. The aim is to study the impact of carrying rare variants in known monogenic obesity genes (gene list: https://panelapp.genomicsengland.co.uk/panels/130/) on the onset of obesity within the UK Biobank population. The methodology will involve comparing carriers and non-carriers in terms of obesity occurrence (BMI), examining interactions with other factors associated with an obesogenic environment (physical activity, diet, sedentary behavior, alcohol consumption, and sleep duration), and polygenic risk scores. The scientific question is: what penetrance can be attributed to these genes in the onset of obesity, what are their modes of transmission, and what are the interactions with other factors?
