Scientists from University College London and Imperial College London in the United Kingdom have identified new genetic locations that might make some people more prone to developing type 2 diabetes.
Using a UCL-developed method of genetic mapping, Maniatis and team examined large samples of European and African American people, summarising 5,800 cases of type 2 diabetes and almost 9,700 healthy controls.They found that the new loci â together with the ones previously identified â control the expression of more than 266 genes surrounding the genetic location of the disease.Most of the newly discovered loci were found outside of the coding regions of these genes, but within so-called hotspots that change the expression of these genes in body fat.Of the newly identified 111 loci, 93 (or 84 percent) were found in both European and African American population samples.
After identifying genetic loci, the next step was to use deep sequence analysis to try to determine the genetic mutations responsible for the disease.Maniatis and colleagues used deep sequencing to further examine three of the cross-population loci with the aim of identifying the genetic mutations. They then investigated a different sample of 94 Europeans with type 2 diabetes, as well as 94 healthy controls.
The researchers found that the three loci coincided with chromosomal regions that regulate gene expression contain epigenetic markers and present genetic mutations that have been suggested to cause type 2 diabetes.Dr Winston Lau said that âOur results mean that we can now target the remaining loci on the genetic maps with deep sequencing to try and find the causal mutations within them. We are also very excited that most of the identified disease loci appear to confer risk of disease in diverse populations such as African Americans, implying our findings are likely to be universally applicable and not just confined to Europeans.âDr Maniatis also highlights the contribution their study brings to the research community:
âNo disease with a genetic predisposition has been more intensely investigated than type 2 diabetes. We have proven the benefits of gene mapping to identify hundreds of locations where causal mutations might be across many populations, including African Americans. This provides a larger number of characterised loci for scientists to study and will allow us to build a more detailed picture of the genetic architecture of type 2 diabetes,â says the lead author.
Dr Andrew also adds, âBefore we can conduct the functional studies required in order to better understand the molecular basis of this disease, we first need to identify as many plausible candidate loci as possible. Genetic maps are key to this task, by integrating the cross-platform genomic data in a biologically meaningful way.â