Molecular Genetics - Polygenic

Our Polygenic Molecular Genetics group consists of a team of 12 scientists, students and technicians that has become internationally recognized as a leader in the genetics of common human traits and conditions. Our focus is on type 2 diabetes and related traits. From 2007 onwards we have led or co-led several important genome wide association studies (GWAS). We jointly led the type 2 diabetes component to the Wellcome Trust Case Control Consortium (WTCCC) efforts. This work, alongside that of other groups, resulted in an unprecedented leap in the understanding of the genetic component to type 2 diabetes and related anthropometric and metabolic traits. In addition to new type 2 diabetes loci (Zeggini et al, Science 2007, Zeggini et al Nature Genetics 2008) we, with collaborators, have helped identify the first robustly associated genetic loci that influence adiposity (Frayling et al. Science 2007,) height (Weedon et al. HMGA2, Weedon et al. Nature Genetics 2007) and reproductive lifespan (Perry et al. Nature Genetics 2009).We have also identified genetic loci associated with important circulating biomarkers including proteins (Melzer et al. PloSGenetics 2008) and anti-oxidants (Perry et al. AJHG 2009).

We are now members of several consortia that are continuing to identify more variants in the human genome that influence important human traits. We are translating these genetic associations into an improved understanding of the biological basis of disease and normal physiology. Examples include Mendelian Randomization studies that provide evidence for a role of sex-hormones in type 2 diabetes (Perry et al. Human Molecular Genetics 2009) and links between fetal growth and type 2 diabetes (Freathy et al. AJHG 2007; Freathy et al. Diabetes 2009, Freathy et al Nature Genetics 2010).

Type 2 Diabetes is caused by a combination of genetic and environmental factors. Despite this the aetiology of type 2 diabetes is still very poorly understood and clinicians are forced to treat the symptoms rather than the causes of the disorder. By finding the genes that predispose to this condition we anticipate that we will help define the underlying pathophysiological pathways involved. A better understanding of aetiology will lead to improved preventative and therapeutic measures.