ABSTRACT
Until recently, much of the medical and public health research on the causes of and risk factors for obesity and its related diseases, including type 2 diabetes mellitus (T2DM) and cardiovascular disease, was focused on two areas: the xed genetic determinants of risk on the one hand and environmental and lifestyle factors such as excessive caloric intake and inadequate energy expenditure on the other. However, the expectations surrounding the explanatory role of genomic variation have become somewhat deated following the rather modest effect sizes of gene variants discovered from genome-wide association studies of metabolic diseases. For example, while fat mass and obesity-associated (FTO) gene polymorphisms have an impact on satiety and affect predisposition to obesity, the association accounts for less than 0.5% of overall variance in body mass index (BMI).1 Meanwhile, public health strategies predominantly focusing on diet and exercise have been relatively ineffective in stemming the relentless rise in obesity rates worldwide.2
