Genetics of Type 2 Diabetes Revealed in Unprecedented Detail

The largest study of its kind into type 2 diabetes has produced the most detailed picture to date of the genetics underlying the condition. Among others, the work was conducted by researchers of the Helmholtz Zentrum München and the German Center for Diabetes Research (DZD). The findings, published in Nature, identify several potential targets for new diabetes treatments, but also reveal the complexity of the disease that needs to be addressed by efforts to develop more personalised strategies for treatment and prevention.

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Source: Fotolia / Leigh Prather

More than 300 scientists from 22 countries collaborated on the study, which analysed the genomes of more than 120,000 people with ancestral origins in Europe, South and East Asia, the Americas and Africa. Among the study team there were scientists from the Institute of Human Genetics, the Institute of Genetic Epidemiology, the Institute of Epidemiology II and the Research Unit of Molecular Epidemiology.

Type 2 diabetes is a growing threat to global health, with one in 10 people either having the disease or predicted to develop it during their lifetime. For any given individual, the risk of developing this form of diabetes is influenced by the pattern of genetic changes inherited from their parents, and environmental factors such as levels of exercise and choice of diet. A better understanding of precisely how these factors contribute to type 2 diabetes will enable researchers to develop new ways of treating and preventing this condition, as well as offering the prospect for targeting those treatments towards those most likely to benefit, and those least likely to suffer harm.

Previous studies have identified over 80 areas in the genome that are associated with type 2 diabetes. However, these studies focused on the role of common DNA differences that appear frequently in the population, and they generally stopped short of identifying exactly which DNA sequence changes, or which specific genes, were responsible for this risk. The new study explored the impact of changes in the DNA sequence on diabetes risk at a more detailed level. Some individuals had their entire genome sequenced while for others, sequencing was restricted to the part of the genome that codes directly for proteins (the exome).

Scientists compared the genetic variation between individuals who had type 2 diabetes and those who did not. This allowed them to test the contribution made by rare, ‘private’ DNA differences, as well as those that are common and shared between people. 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. Some researchers had thought that genetic risk would instead be dominated by rare changes, unique to an individual and their relatives.

This finding means that future efforts to develop a personalised approach to treatment and prevention will need to be tailored toward an individual’s broader genetic profile, non-genetic risk factors and clinical features. Researchers also identified over a dozen type 2 diabetes risk genes where the DNA sequence changes altered the composition of the proteins they encode. This implicates those specific genes and proteins directly in the development of type 2 diabetes.