Investigation of the regulatory hot spots identified for type 2 diabetes

The complex causal chain between a gene and its effect on disease susceptibility cannot be unravelled until the casual changes have been localised in the DNA sequence. By exploiting high-resolution population-specific genetic maps, we have recently identified 111 additional locations of disease susceptibility, 93 of which are found in European and African-American people and 18 that are specific to Europe. We also refined previously identified type 2 diabetes signals and showed that many of these are also risk loci in African-Americans. We have obtained a precise location for the implicated functional variants and we were able to identify that the majority of the disease locations appear to confer risk of type 2 diabetes by acting as expression quantitative trail loci (eQTL) that regulate adipose expression levels of a large number of cis-regulated genes.

Our aim is to further characterise in detail all the 111 novel and previously found loci by effectively integrating all our causal location estimates together with cell-specific regulatory annotation and chromatin modifications. So far we have only used adipose tissue but we will also investigate all our disease and co-localised eQTL locations for tissue specificity by performing gene expression analyses in other tissues relevant to type 2 diabetes.