Grant: Project Grant

Obesity is associated with an increased risk of cardiovascular disease (CVD) and type 2 diabetes. However, the obesity trait is highly variable from one individual to another. Genetics and epigenetic factors may contribute to this inter-individual variability. In the past decades, several international research efforts we were part of have taken on the challenge of decoding the genome and epigenome sequences associated with obesity and its related metabolic complications. However, most of these diseases are influenced by several genes each having only a small effect on its own. Polygenic approaches dealing with mass genetic and epigenetic data access more of the variance of these traits and can better predict individual risks of obesity and its metabolic complications, and more importantly treatment success. Weight loss and metabolic improvements after an anti-obesity surgery are highly variable and remain a poorly studied phenomenon. Time and efforts must be devoted to the identification of determinants of this large inter-individual variability in order to direct the patient to the treatment option with the greatest chance of success. We then propose to find a genetic/epigenetic set of determinants of body weight loss and metabolic recovery after bariatric surgery that may be used to develop applications to target the best surgical options for a patient. The specific aims are: Specific Aim 1: To derive a polygenic risk score (PRS) associated to the progression of weight loss and metabolic outcomes after a bariatric surgery. Specific Aim 2: To assess the potential of a blood DNA methylation risk score (MRS) to predict body weight loss and metabolic improvements after a bariatric surgery. Specific Aim 3: To test whether a combination of genetic and epigenetic determinants can better predict post-bariatric surgery outcomes than either a PRS or a MRS individually. These high-potential, new research avenues merit further investigation.