In the largest genome-wide association study of type 2 diabetes to date, an international team of researchers, led by a Massachusetts Amherst genetic epidemiologist, found 1,289 genetic markers associated with type 2 diabetes. (of which 145 were newly identified. ) and created risk scores for diabetes complications.

In research published Monday, Feb. 19, in the journal The nature In a move that advances understanding of the inheritance of type 2 diabetes, scientists used state-of-the-art computational methods to identify eight distinct mechanistic clusters of genetic variants associated with the disease. They also explored the relationship between individual clusters and diabetes complications.

“We tried to figure out some mechanism of how these genetic variations are working — and we did,” says co-senior author Cassandra Sprinklin, assistant professor of biostatistics and epidemiology in the School of Public Health and Health Sciences. “

Ultimately, the goal is to identify potential genetic targets to treat or treat the chronic metabolic disease that affects more than 400 million adults worldwide and is sometimes debilitating, according to the International Diabetes Federation.

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

“We found eight clusters of variants associated with type 2 diabetes that have also been associated with other risk factors for diabetes – such as obesity and liver-lipid metabolism – suggesting a mechanism for how the variants may cause diabetes. are working,” says Spracklen. “We then asked if these clusters are also associated with complications of type 2 diabetes? And we found that many of them are also associated with vascular complications, such as coronary artery disease and ultimately diabetic nephropathy.”

Although effective treatments are available for type 2 diabetes, the choice of an individualized medication is still limited. For many people with the disease, treatment strategies still rely on trial and error. Being able to better understand the mechanisms of the disease will help predict individuals’ risk of type 2 diabetes and allow for early intervention.

“We’re trying to understand how diabetes develops,” Sprecklin says, adding that the new study is not available in earlier genome-wide association studies published in Nature Genetics in 2022. Includes data from, for which Sprinklin was co-first author. “And we’re trying to better understand how these genetic variations are actually working within the biological tissue or at the cellular level, which could ultimately lead to new drug targets and treatments.”

Senior corresponding author Eleftheria Zigny, director of the Institute of Translational Genomics at Helmholtz Munich and professor at the Technical University of Munich, notes that scientists need to review extensive patient data and gain a comprehensive understanding of genomic risk variants. Cooperation between is essential.

“The genetic information in our cells holds secrets to the risk, progression and complications of many diseases,” she says. “Our work leads to a better understanding of the biological mechanisms that cause the disease. A better understanding of the risk of developing complications of type 2 diabetes may aid in early interventions to delay or even prevent these debilitating medical conditions. Is.”

The paper concludes, “Our findings … may offer a pathway to improve global access to genetically informed diabetes care.”