A study analyzes the genetics of type 2 diabetes. During the last years, intense efforts have been dedicated to catalog all genetic variations that influence the risk of developing type 2 diabetes, as well as their biological role in this pathology.

In addition, as a common and complex disease, type 2 diabetes is located in the center of a classic debate about whether the genetic differences that influence the predisposition to these diseases are relatively common and shared by populations, or on the contrary, ifThese are rare events.

Multiple studies of the association of complete genomes, in which genetic variation was compared in patients with type 2 diabetes with respect to that of control individuals, have allowed identifying genetic variants common to the disease.

These variants explain only a proportion of the variation of the disease attributed to genetic factors, so there are still components to identify.In addition, so far, the effect of rare variants had not been analyzed in depth.

The objective of the new work, published in Nature was to evaluate the influence of the rare variants in the development of type 2 diabetes and estimate whether through them it could be explained part of the variation not explained by the common variants already previously identified.

The contribution of rare variants in type 2 diabetes is minority with respect to common variants, the study points out.
"Our study has led us to the most complete understanding of the genetic architecture of type 2 diabetes," says Michael Boehnke, one of the work directors."Through this in -depth analysis we have obtained a more complete image of the number and characteristics of the genetic variants that influence the risk of type 2 diabetes"

For the work, the sequencing of the complete genome of more than 2,500 people of European descent, with and without diabetes, as well as sequencing of the exom, the coding part of the genome, in about 13,000 people with ancestry of another 5 populations.In addition, the team evaluated the genetic variation in 110,000 more individuals.The achievement of a such majority project required the participation and collaboration of two large research consortiums in type 2 diabetes, the GOT2D and the T2D-genes, in which 300 researchers from 22 different countries have worked.

The results of the work offer the most detailed analysis until the moment of the genetic architecture of type 2 diabetes. The most relevant information is that the genetic variants associated with type 2 diabetes are surprisingly common and are located in regions already identified through studiesof full genome association.

The data obtained in the sequencing suggest that the rare variants do not have such an important role as expected in the predisposition to the disease.According to the authors, low frequency risk alleles contribute more to early appearance forms.The sequencing of genomes and exams, carried out in the project, has identified new variants of this type that influence the disease.However, its contribution to the disease is minority with respect to common variants.

"While low frequency variants certainly influence the risk of type 2 diabetes, our results indicate that common variants shared through populations explain most of the risk to type 2 diabetes," Boehnke points out.

“Our study tells us that most people have a risk of type 2 diabetes due to hundreds or even thousands of genetic variants,Typically shared in the populations, ”says Jason Flannick, a researcher at the Broad Institute of Harvard and Massachusets Institute of Technology and in the Massachusetts General Hospital.“While this wide range of genetic risk could challenge our efforts to carry out precision medicine, our consortium offers a set of data that can be accessed publicly, unprecedented in scope, for researchers around the world,To advance our knowledge of type 2. "

To solve the complete puzzle of the genetic bases of type 2 diabetes, it will still be necessary to investigate more.The authors of the work, conclude that “the integration of the biological knowledge obtained from the genetic associations of type 2 diabetes with the common or rare genetic variants in a unified image of the disease pathophysiology will be necessary to completely understand the bases ofIt is common but challenging disease. "

Reference: Fuchsberger C, et al.The Genetic Architecture of Type 2 Diabetes.Nature2016 Jul 11. Doi: DOI: 10.1038/Nature18642.

Source: U-M, International Research Team Explore Genetic Architecture of Type 2 Diabetes. Link