The extent of the genetics underlying type 2 diabetes has been uncovered in the largest global study of its kind, it was announced last night.
The research, which involved more than 300 scientists from 22 countries and is published today in Nature, identified a number of potential targets for new diabetes treatments and increases understanding of the condition.
The team analysed the genomes of more than 120,000 people, moving on from previous studies that identified more than 80 areas in the genome associated with the condition, and saw them exploring at a highly detailed level the impact of changes in the DNA sequence on diabetes risk.
While some participants had their entire genome sequenced, others had the exome sequenced and scientists compared the genetic variation between individuals with type 2 diabetes and who do not have the condition to check what, if any, rare, ‘private’ DNA differences made an impact.
They found that most of the genetic risk of type 2 diabetes can be attributed to common, shared differences in the genetic code, each of which contributes a small amount to an individual’s risk of disease.
Researchers also identified more than a dozen type 2 diabetes risk genes in which changes to the DNA sequence altered the composition of the proteins they encode. For example, a variant in the TM6SF2 gene altered the amount of fat stored in the liver, which in turn results in an increase in the risk of type 2 diabetes.
Senior author Mark McCarthy, from the Wellcome Trust Centre for Human Genetics at the University of Oxford, said: "This study highlights both the challenges we face, and the opportunities that exist, in resolving the complex processes underlying a disease such as type 2 diabetes. In this study, we have been able to highlight, with unprecedented precision, a number of genes directly involved in the development of type 2 diabetes.
"These represent promising avenues for efforts to design new ways to treat or prevent the disease."
Joint senior author Professor Michael Boehnke, Richard G Cornell Distinguished University Professor of Biostatistics, director, Center for Statistical Genetics, University of Michigan School of Public Health, added: "Our study has taken us to the most complete understanding yet of the genetic architecture of type 2 diabetes. With this in-depth analysis we have obtained a more complete picture of the number and characteristics of the genetic variants that influence type 2 diabetes risk."
Jason Flannick, co-lead author and senior group leader at the Broad Institute of Harvard and MIT and Research Associate at the Massachusetts General Hospital, said: "Our study tells us that genetic risk for type 2 diabetes reflects hundreds or even thousands of different genetic variants, most of them shared across populations.”
The genetic architecture of type 2 diabetes. Nature 11 July 2016 [abstract]
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