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Mapping the genomic landscape of type 2 diabetes

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In the largest genome-wide association study of type 2 diabetes to date, an international research team co-led by University of Massachusetts Amherst genetic epidemiologists identified 1,289 genetic markers associated with type 2 diabetes, including 145 newly identified ) and generated a risk score for diabetic complications.

Research results published Monday, February 19 in the journal Nature To advance our understanding of the heritability of type 2 diabetes, scientists used a cutting-edge computational approach to identify eight distinct mechanistic clusters of genetic variation associated with the disease. They also found associations between individual clusters and diabetic complications.

We set out to elucidate some of the mechanisms of how these genetic variations function, and we have succeeded. ”

Cassandra Spracklen, co-senior author, assistant professor of biostatistics and epidemiology, School of Public Health and Health Sciences

The ultimate goal is to identify potential gene targets to treat or even cure the sometimes debilitating chronic metabolic disease that affects more than 400 million adults worldwide, according to the International Diabetes Federation. It is said that

The study, born out of the newly established Type 2 Diabetes Global Genomics Initiative, includes data from a highly diverse group of more than 2.5 million people, 428,452 of whom have type 2 diabetes. .

“We discovered eight clusters of type 2 diabetes-associated mutations that are also associated with other diabetes risk factors such as obesity and hepatic lipid metabolism. This may explain how the mutations act to cause diabetes. “This suggests a possible mechanism for this,” Professor Spracklen said. “We then asked whether these clusters were also associated with complications of type 2 diabetes. And some of them were also associated with vascular complications such as coronary artery disease and end-stage diabetic nephropathy. I found out that it is.”

Although effective treatments exist for type 2 diabetes, personalized precision medicine options remain limited. For many people with this disease, treatment strategies still rely on trial and error. A better understanding of disease mechanisms will allow us to predict an individual’s risk of developing type 2 diabetes and allow for early intervention.

“We’re trying to understand how diabetes develops,” Spracklen said, adding that the new study includes a previous study published in Nature Genetics in 2022, of which Spracklen is co-lead author. It added that it included data from cohorts not available in genome-wide association studies. “And we are working to better understand how these genetic mutations actually act within living tissues or at the cellular level, which will ultimately lead to new drug targets and treatments. There is a possibility.”

Senior corresponding author Elefteria Zeggini, director of the Translational Genomics Institute at Helmholtz München and professor at the Technical University of Munich, evaluated vast amounts of patient data to achieve a comprehensive understanding of genomic risk variants. He points out that cooperation among scientists is essential to achieve this goal.

“The genetic information in our cells holds secrets about the risk, progression, and complications of many diseases,” she says. “Our research will lead to an improved understanding of the biological mechanisms that cause the disease. A deeper knowledge of the risk of developing type 2 diabetes complications could help slow or even prevent these debilitating conditions. It helps us put in place early intervention to help.”

The paper concludes that “our findings…may provide a path to optimizing global access to genetically informed diabetes treatments.”


Reference magazines:

Kazuya Suzuki other. (2024). Genetic causes of heterogeneity in the pathophysiology of type 2 diabetes. Nature. doi.org/10.1038/s41586-024-07019-6.

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