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Genetics of type 2 diabetes revealed in unprecedented detail

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Posted July 13, 2016

A comprehensive investigation of the underlying genetic architecture of type 2 diabetes has unveiled the most detailed look at the genetic differences that heighten a person’s risk for disease development.

The findings, published today in the journal Nature by an international team of more than 300 scientists led by the University of Oxford, the Broad Institute, and the University of Michigan, reveal the complexity of the disease in more detail than previously appreciated, but also identify several promising targets for new treatments.

Type 2 diabetes is a global health concern, with approximately ten percent of the world’s population diagnosed with the disease or likely to develop it in their lifetime. Previous studies into the genetics of diabetes risk have identified over 80 areas in the human genome associated with type 2 diabetes; however, it remains unknown exactly how these genetic changes, known as variants, are distributed among populations and how they lead to increased risk. Functional explanations for these risk variants have been particularly elusive because most of them fall outside the coding region of genes, and are presumably involved in gene regulation.

Using DNA sequencing in more than 120,000 people with ancestral origins in Europe, South and East Asia, the Americas and Africa, the authors, including Francis Collins, M.D., Ph.D., director of the National Institutes of Health and head of the Molecular Genetics Section at the National Human Genome Research Institute, evaluated the genome at a greater level of detail than had been previously attempted for type 2 diabetes. Some individuals had their entire genome sequenced while for others the researchers focused on the part of the genome that codes directly for proteins, known as the exome. The researchers then compared the genetic changes between affected and healthy participants.

The findings suggest that most of the genetic risk of type 2 diabetes can be attributed to common, shared genetic variants – each contributing a small amount to an individual’s risk of the disease – rather than many rare variants unique to individuals. This resolves a question about the genetics of type 2 diabetes that has puzzled researchers for decades.

The researchers also identified over a dozen genes in affected participants where changes in the DNA sequence altered the structure or composition of the proteins they encode, suggesting that those genes and proteins are directly involved in the development of the disease and providing important clues to the mechanism by which they confer risk. That, in turn, provides possible clues to new drug targets.

Results from this study suggest that any personalized approach to treatment and prevention of type 2 diabetes will need to be tailored on the basis of an individual’s broader genetic profile, as well as environmental factors.

Source: NIH

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