What Our Genetic Information Tells Us About Type 2 Diabetes Risk and Complications

The genetic information in our cells harbors secrets about the risks, progression, and complications of many diseases. With hundreds of millions of patients worldwide, identifying and understanding genetic risk for type 2 diabetes is of particular interest. In collaboration with an international team of scientists, Prof. Eleftheria Zeggini from the DZD-partner Helmholtz Munich and the Technical University of Munich (TUM) has conducted a comprehensive study with data from millions of individuals. Their research unveiled over 600 disease-associated genetic loci and generated risk scores for diabetes complications. The insights from the largest type 2 diabetes genome-wide association study to date are now published in 'Nature'.

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The prevalence of diabetes continues to increase significantly. According to the WHO, over 400 million people worldwide are living with type 2 diabetes (T2D), a disease with various symptoms and causes. Even though effective treatment options are becoming available, the option for precision medicine is still limited. For many patients, treatment strategies still rely on trial and error. Importantly, T2D can lead to numerous secondary health issues, and there is a critical need for a deeper comprehension of the disease mechanisms to predict the risk of T2D complications and intervene early.

Largest Study on Genetic Risk for Diabetes Now Published
Collaboration among scientists is essential for evaluating vast patient data and achieving a comprehensive understanding of genomic risk variants. Helmholtz Munich scientists are part of the newly formed Type 2 Diabetes Global Genomics Initiative (T2D-GGI). The first outcome of the initiative is the largest genome-wide association study (GWAS) to date. GWAS is a scientific method used to find genetic variation associated with a disease.

The new study encompasses over 2.5 million individuals (428,452 with T2D). Eleftheria Zeggini, senior corresponding author of the study, remarks: “We have carried out the largest genome-wide association study for type 2 diabetes as a collaborative achievement of hundreds of researchers from across the globe. We have found novel genetic risk loci for the disease and have constructed genetic risk scores that are associated with harmful complications.”

The authors used cutting-edge computational approaches to integrate data across multiple -omics modalities. They identified eight distinct mechanistic clusters of genetic variants associated with T2D and discovered associations between individual clusters and diabetes complications.
“Our work leads to an improved understanding of disease-causing biological mechanisms. Better knowledge of progression risk for T2D complications can help put in place early interventions to delay or even prevent these debilitating medical conditions,” says Eleftheria Zeggini.

Suzuki et al. (2024): Genetic drivers of heterogeneity in type 2 diabetes pathophysiology. Nature. DOI: 10.1038/s41586-024-07019-6