In the world's largest genome study on a disease, bioinformatician Christian Fuchsberger from Eurac Research and an international team of scientists investigated the genome of thousands of people. The researchers identified four genes with rare variants that affect diabetes risk. The data suggests that hundreds more genes will likely be identified in the future. These genes and the proteins they encode are potential targets for new medicines, and may guide researchers to better understand and treat disease.
Type 2 diabetes, the most common form of diabetes, is caused by obesity and lack of exercise and is therefore considered a typical lifestyle disease. More than 20,000 patients with type 2 diabetes are currently treated in South Tyrol. However, the tendency to develop this form of diabetes is also genetically determined and very rare variants, which occur in at most one out of every thousand people, are a valuable resource to understand the disease. Scientists can only identify such rare genetic variants on the basis of very large numbers of cases and previous studies have been too small in scale for this purpose. However, an international study, recently published in the journal Nature, has analyzed the protein-coding genome of nearly 46,000 people, linking rare DNA alterations to type 2 diabetes. The results have been collected in an open-access database and will be of great value to better understand and treat disease.
More than 150 scientists from 22 countries have analyzed the exomes, that is, only those regions in the genome that code for proteins, of almost 21,000 people with type 2 diabetes and 24,000 healthy controls. This is the largest genome study ever carried out on a disease (the largest type 2 diabetes study to date examined the exomes of 10,000 people). The large number of cases allowed the scientists not only to identify several rare genetic variants associated with diabetes, but also to correct previous assumptions: For example, they were able to recognize that a gene previously thought to increase one’s risk of diabetes, in fact protects carriers from the disease.
Bioinformatician Christian Fuchsberger explains why it is so important for drug development to identify such variants: "It is irrelevant that these variants are so rare: If you understand their mechanism, you can try to reproduce them with a drug and thus help millions of people.” Fuchsberger, who received the South Tyrolean Research Prize last year, was one of the leading authors of this study.
All of the team’s results are publicly available online through the Type 2 Diabetes Knowledge Portal http://www.type2diabetesgenetics.org
/, enabling scientists around the world to access and use the information for their own research.
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