New scientific resource will help uncover the genetic basis of type 2 diabetes

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Knowing the gene behind a given genetic association is the first step in identifying potential drug targets or in better understanding the physiology of different types of diabetes.

Josep M. Mercader, PhD
Diabetes Unit and Center for Genomic Medicine
Massachusetts General Hospital

BOSTON – Many variants of the human genome have been linked to type 2 diabetes, but since most are not found in the genes that code for proteins, it’s unclear how they might cause the disease. Now, an international team, including researchers from Massachusetts General Hospital (MGH), has developed a resource to help uncover the impact of these genetic variants.

The work, which is described in Cell reports, is based on the knowledge that abnormalities in groups of pancreatic cells called islets, which produce and release hormones that regulate blood sugar, lead to the development of type 2 diabetes. Unfortunately, however, it is very difficult to obtain samples. human islets. To meet this challenge, scientists from Spain, Belgium, Italy, Sweden, Finland, United Kingdom and United States have come together to obtain more than 500 human islet samples from patients with or non-type 2 diabetes patients and to extract genomic and gene expression data from these samples. With this data, the researchers created what they named TIGER (for Translational human pancreatic Islet Genotype tissue-Expression Resource).

The research required the collection and examination of an enormous amount of information, which was made possible through the use of high-performance computing resources and new statistical methods.

TIGER’s analyzes revealed that certain genetic variants in the islets of patients with type 2 diabetes control the expression of particular genes. So far, 32 new genes have been identified that may contribute to the risk of type 2 diabetes.

“This resource will be very useful in identifying genes that may be linked to genetic variants that we have found associated with type 2 diabetes,” says lead co-author Josep M. Mercader, PhD, researcher in the Diabetes Unit of the ‘MGH and Center for Genomic Medicine. “Knowing the gene behind a given genetic association is the first step in identifying potential drug targets or in better understanding the physiology of different types of diabetes.

TIGER data is publicly available and easily accessible to the diabetes research community through the TIGER web portal (tigre.bsc.es).

“We are proud to now be able to share this wealth of data with the scientific community in a way that is easily accessible to all researchers in the field of type 2 diabetes, without the need for computer or bioinformatics expertise,” says the co – principal author Lorena Alonso, from the Barcelona Supercomputing Center, Spain, one of the developers of the TIGER portal.

Co-lead authors include Ignasi Moran, PhD, from the Barcelona Supercomputing Center and Anthony Piron, from the Université Libre de Bruxelles. Co-lead authors include Miriam Cnop, MD PhD, of the Université Libre de Bruxelles, and David Torrents, PhD, of the Barcelona Supercomputing Center.

Other co-authors include Marta Guindo-Martínez, Sílvia Bonàs-Guarch, Goutham Atla, Irene Miguel-Escalada, Romina Royo, Montserrat Puiggròs, Xavier Garcia-Hurtado, Mara Suleiman, Lorella Marselli, Jonathan LS Esguerra, Jean-Valéry Turatsinze, Jason M. Torres, Vibe Nylander, Ji Chen, Lena Eliasson, Matthieu Defrance, Ramon Amela, MAGIC, Hindrik Mulder, Anna L. Gloyn, Leif Groop, Piero Marchetti, Decio L. Eizirik and Jorge Ferrer.

This work was supported by the European Union’s Horizon 2020 research and innovation program T2Dsystems under grant agreement No 667191.

About Massachusetts General Hospital
Massachusetts General Hospital, founded in 1811, is Harvard Medical School’s first and largest teaching hospital. The Mass General Research Institute leads the nation’s largest hospital-based research program, with annual research operations of over $ 1 billion, and includes more than 9,500 researchers working in more than 30 institutes, centers and departments. In August 2021, Mass General was named # 5 in the American News and World Report list of “America’s best hospitals”.


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