Scheme: Wolfson Research Merit Awards
Organisation: University of Exeter
Dates: Oct 2007-Sep 2012
Summary: Our team focuses on understanding the genetic component to common diseases and human traits such as type 2 diabetes and obesity. We are also leading studies to identify the genetic factors that influence where an individual is on the scale of normal variation - for example their height or body mass index.
The last three years have resulted in enormous progress in this field. We now know of >500 regions of the human genome where common variation influences human diseases and normal variation. Further work is needed to understand how these variations alter gene function, but they are already providing important biological insights. Genetic studies of type 2 diabetes have shown that a) reduced beta cell function has a greater role in disease predisposition than insulin resistance, although genetic factors exist for both pathways; b) there is a genetic link between reduced birth weight and type 2 diabetes - perhaps suggesting that interventions to reduce birth weight are unlikely to reduce the risk of diabetes; c) there is a causal link between levels of sex hormone binding globulin (SHBG) and type 2 diabetes - contrary to prevailing views that altered SHBG was simply secondary to diabetes; d) there is a genetic link between circadian rhythm and diabetes - providing evidence that disrupted sleep patterns may influence diabetes; e) there is a genetic, and therefore biological, difference between physiological (normal) and pathophysiological (diabetes) glucose levels - different gene variants influence non-diabetic fasting glucose levels compared to the gene variants influencing type 2 diabetes progression.