The Genetic Architecture of Type 2 Diabetes
Genetic disease or a question of lifestyle? So far, the question of hereditary components in type 2 diabetes has remained open. A paper published in ‘Nature’ now concludes that, contrary to model predictions, the influence of rare sequence variants in the human genome on diabetes risk is low. Rather, most genetic risk factors occur in regions that exist in a similar way in many people.
A team of more than 300 experts, including scientists from the German Center for Diabetes Research (DZD) at Helmholtz Zentrum München, analyzed the genome of 120,000 people with genetic origins in Europe, South and East Asia, North and South America and Africa. In the study they compared the sequence data of people with and without type 2 diabetes.
The sequence analysis of the whole genome as well as the exome – the subset of DNA that encodes proteins – in 15,700 test subjects resulted in 126 sequence variants that are significantly associated with diabetes risk. These DNA regions are in four genes: TCF7L2, ADCY5, CCND2 and EML4, whereby the first three have already been shown to be associated with diabetes risk.
The investigation of variants in the coding sequence sections in the DNA of more than 90,000 people also confirmed the results of previous genome-wide association studies (GWAS). For a single additional gene, MTMR3, the scientists were able to show a previously unknown association of a coding sequence variant with diabetes.
The results of these comprehensive analyses suggest that the genetic causes for diabetes risk in the population can be ascribed to frequent sequence variants in the DNA.
The genetic architecture of type 2 diabetes.
Fuchsberger C., et. al. Nature (2016). Jul 11. doi: 10.1038/nature18642.